Dedication

To Pus It made me what I am.

Chapter One

Past TB. Current Treatment?

Sep 3, 2014

There was a time before antibiotics when all the physician could do was support the patient and watch the patient get better. Or not.

Seventy years ago, the patient developed TB, probably from a family member. He tells me that he went to the doctor every week for a chest X-ray and blood work. That is a lot of radiation to a kid, and as an adult, he developed a non-Hodgkins lymphoma. Related? I get the impression it is more than the current radiation we give kids.

Overall, this review, based on 12 case-control studies and 6 cohort studies, shows no significant association between exposure to medical diagnostic radiation exposure and childhood cancer risk.

So probably not.

Eventually, he moved to Texas where he improved, perhaps in part to the sunshine raising his vitamin D levels:

There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). data-preserve-html-node="true" Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). data-preserve-html-node="true"

Or not. But he never received antibiotics for TB and, at one point had a course of rituximab to cure the lymphoma. No TB recurrence, perhaps because rituximab is a bit safer in TB patients?

After a sufficient time of follow-up, we have observed that Rtx seems to be safer and efficient in the treatment of active RA and TB.

Or not. Now he is sent to me with the question of what to do? He had a CT of his chest as part of his lymphoma evaluation, and it only shows a right middle lobe Ghone complex. Nothing in the upper lobes. No scar, no cavity. Was his TB back in the day right middle lobe primary disease, the initial pneumonitis after inhalation, which usually improves? I suspect so given the CT, but the old records and chest X-rays are not available.

So now what? Got me. We talked over the risk-benefits of treatment for latent TB, and he did not want to take medications. I figured with the negative CT and the stress test of lymphoma and rituximab, it was unlikely he would get active TB, but if immunosuppression was likely in the future that he should get prophylaxis.

I have had this question in the past: old cured active TB in the pre-antibiotic era and no antibiotics when they became available. Treat? I can't find an official recommendation, although I bet one exists.

Sometimes I treat, sometimes I don't. It depends on the total of the risks and the benefits.

Rationalization

Arch Pediatr. 2012 Jan;19(1):64-73. doi: 10.1016/j.arcped.2011.10.023. Epub 2011 Nov 29. [Diagnostic radiation exposure in children and cancer risk: current knowledge and perspectives].

http://www.ncbi.nlm.nih.gov/pubmed/22130615

J Infect Dis. 2014 Sep 1;210(5):774-83. doi: 10.1093/infdis/jiu121. Epub 2014 Mar 4. The seasonality of tuberculosis, sunlight, vitamin d, and household crowding.

http://www.ncbi.nlm.nih.gov/pubmed/24596279

PLoS One. 2013;8(3):e57752. doi: 10.1371/journal.pone.0057752. Epub 2013 Mar 6. Tuberculosis incidence correlates with sunshine: an ecological 28-year time series study.

http://www.ncbi.nlm.nih.gov/pubmed/23483924

BMJ Case Rep. 2013 Jan 21;2013. pii: bcr2012006585. doi: 10.1136/bcr-2012-006585. Rituximab seems to be a safer alternative in patients with active rheumatoid arthritis with tuberculosis.

http://www.ncbi.nlm.nih.gov/pubmed/23341582

Proc R Soc Med. Aug 1944; 37(10): 585–588. PMCID: PMC2181417 Section for the Study of Disease in Children: Held at Highwood Hospital, Brentwood The Importance of Primary Pulmonary Tuberculosis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2181417/

Chapter Two

Why? How Long?

Sep 8, 2014

The diagnosis is not in question — a right middle lobe lung abscess. The patient had been ill for about a month with mostly fatigue and weight loss, and given the size of the abscess, almost 6 cm across, it had been there for a while. Cultures grew S. anginosus, one of the milleri group of abscess causing Streptococci.

The question that is at issue is why. Dentition is not that bad, and he has no loss of consciousness or aspiration. He doesn't drink or (currently) smoke. And his breath isn't foul, so I doubt anaerobes are an issue.

He does snore, but I can find no references to suggest that either sleep apnea or snoring has ever been associated with lung abscess, which kind of surprises me since the choking/aspiration of sleep apnea should lead to the occasional lung abscess.

No cancer was found on studies, but that is not completely reassuring.

We present two patients with a pulmonary abscess caused by an underlying lung cancer. Although in both cases, the differential diagnosis was malignancy at first presentation, the diagnosis could not be made definitively prior to surgery, despite intensive investigations with even CT guided biopsies and mediastinoscopy.

What they want to know from me is how long to treat.

The answer? Who knows. The duration of therapy is one of the least satisfactory metrics in ID. Part of the problem is not all infections, hosts, and organisms are the same, and some get better faster than others. Many durations of therapy are an average that works most of the time for most patients.

For some infections, the duration is based on the least duration you can give to get an acceptable cure rate: UTI comes to mind.

For other infections, the duration is what provides the best cure rate, and if you treat longer, it will not improve cure rates, you have to cut the infection out. Endocarditis comes to mind. If six weeks of nafcillin doesn't work, the valve almost certainly needs to come out.

For most infections, the duration is either 10, as we have ten fingers or a multiple of 7 as we have seven days in a week. I am thankful we are not Sumerian, who had a sexagesimal (base 60) counting system. We would be giving antibiotics forever.

The real answer for how long to treat is until the infection is cured, but how to define cure is not as easy as saying 10 or 21 days. In this case, as in so many collections of pus, the duration is until the abscess is gone.

My rule of thumb: 2 cm across will take four weeks and add a week per centimeter, a rule pulled out of my experience and completely validated by confirmation bias. And that's assuming drainage of some sort.

Rationalization

Clin Infect Dis. 1995 Dec;21 Suppl 3:S238-43. The Streptococcus milleri group as a cause of pulmonary infections.

http://www.ncbi.nlm.nih.gov/pubmed/8749672

A pulmonary abscess, beware of lung cancer! Respiratory Medicine CME Volume 4, Issue 4, 2011, Pages 157–159

http://www.sciencedirect.com/science/article/pii/S1755001711000376

Thorax 1995;50:1093-1096 doi:10.1136/thx.50.10.1093 Research Article Streptococcus milleri pulmonary disease: a review and clinical description of 25 patients.

http://thorax.bmj.com/content/50/10/1093.short

POLL RESULTS

I base my actions on the number

• 7: 19%
• 10: 5%
• 42: 30%
• 3.141592654. It's as easy as…: 26%
• I: 9%
• Other Answers: 11%
  • Googol: The internet knows all.
  • 123
  • whatever
  • The number of the beast works pretty well.
  • 4-6 weeks for deep-seated/ undrained abscesses

Chapter Three

Uncertain Certainty

Sep 10, 2014

Life used to be simpler. In the old days, I often had no idea what was going on in a patient. I mean nothing. Not a clue. I knew they were ill, that they probably had an infection, but I had a limited number of diagnostic and therapeutic options.

I have mentioned before that my first consult in practice died and at autopsy had cardiac Aspergillus. I may have made that diagnosis today as I have antigen testing for Aspergillus that I lacked in 1990. But at the time, I had no way to make the diagnosis.

But now, I have more diagnostic tests and therapeutic options, but it has made me more uncertain in my certainty.

Two patients were acting clinically infected, both immunoincompetent for different reasons — one with masses in the upper lobe, one with ground glass opacities in all lung fields. CTs and bronchoscopies and biopsies show no organisms, and cultures and histopathology is consistent with infection but no organisms are seen or isolated. I have no further diagnostic tests to order to find the infection.

They both have persistently positive 1-3 beta-D-glucans. Not low, either. Both greater than 400.

As best I can tell, they do not have any of the fungi that would lead to a positive test, although cultures are cooking.

The Fungitell beta-D Glucan assay detects (1,3)- beta-D-glucan from the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, Pneumocystis jiroveci.

The Fungitell beta-D Glucan assay does not detect certain fungal species such as the genus Cryptococcus, which produces very low levels of (1,3)- beta-D-glucan, nor the Zygomycetes, such as Absidia, Mucor, and Rhizopus, which are not known to produce (1,3)- beta-D-glucan. Studies indicate Blastomyces dermatitidis is usually not detected due to little (1,3)- beta-D-glucan produced in the yeast phase.

Neither have a reason for a false positive

Caution is also warranted in the presence of factors that could increase BDG levels for reasons other than IFI, such as hemodialysis with cellulose membranes, administration of human blood products (immunoglobulins or albumin), use of such antibiotics as amoxicillin-clavulanate or piperacillin-tazobactam, presence of serious bacterial infections, use of surgical gauzes containing glucan, or severe mucositis.

So it must be the real deal, but what do I treat with? An azole? Which one? Drug-drug interactions with voriconazole and posaconazole are significant. Micafungin will not treat some of the infections well enough. And amphotericin? My drug of choice, but both patients have few functioning nephrons as is.

I am certain they have a fungal infection, but I am uncertain as to which one, and what to do about it. I have uncertain certainly. Very aggravating and very Rumsfeldian.

Rationalization

β-D-Glucan Assay for the Diagnosis of Invasive Fungal Infections: A Meta-analysis. http://cid.oxfordjournals.org/content/52/6/750.full

POLL RESULTS

I

• am comfortable with uncertainty. 22%
• am uncomfortable with uncertainty. 22%
• oblivious. Less stressful. 17%
• prefer certainty over reality. I watch Fox. 6%
• prefer reality over certainty. 22%
• Other Answers 11%
  • am what I yam.
  • think, therefore I am.
  • demand rigidly defined areas of doubt and uncertainty. It helps that my wife is a good existential thinker.
  • prefer reality, but it is different for each of us

Chapter Four

Grumpy and Getting Worse with Age

Sep 15, 2014

I am having more senior moments. Word finding is more of an issue. I just stop mid-sentence because I cannot find the word I want. The other day I was picking up my son at a meeting and going down the steps to leave, and I opened the door to the janitor's closet rather than the front door of the building I was exiting. That led to no end of amusement on the part of my son.

Another sign I am getting older and grumpier is that issues I would not have given a second thought now irritate the hell out of me. Especially how others use antibiotics.

Part of the issue is I have 24 years under my expanding belt, and currently everyone else is comparatively inexperienced and motivated by a FUD that I do not experience. Been there, done that.

For the youngsters, it is don’t just stand there, do something. For me, it is don’t just do something, stand there. Because so much of the time, if the patient is stable, the best intervention is waiting.

But oh, no, there is a fever or another minor change, and by god, above all, the antibiotics have to be changed. So the antibiotics are changed.

At any given time, most docs are unable to remember more than two antibiotics, and currently, it appears to be Zosyn and vancomycin. Perhaps not the best choice:

The results of this study suggest that there may be an association between piperacillin-tazobactam and vancomycin combination therapy and increased incidence of AKI.

When a patient is going south from sepsis, you have to kill everything that may be killing the patient. All too often an antibiotic change is made because of physician (not diagnostic) uncertainty or lack of source control rather than the patient being on the wrong antibiotic. BTEW, antibiotics will not drain an abscess. True story. But it is the antibiotics that are changed, and not always for the better.

Changed, more often than not, to Zosyn and vancomycin, and everyone is reassured by big gun, strong, powerful antibiotics except the ID doc, who is only irritated. As you know, using the terms big gun, strong, or powerful to describe antibiotics is 100% sensitive and specific that the speaker in an idiot who knows nothing about the proper use of antibiotics.

We do not yet have a formal antibiotic stewardship program in my hospital systems. I have done some preliminary work towards that goal and see room for improvement in antibiotic use. But the problem with most antibiotics stewardship program is that interventions are not made until 48 hours into the antibiotic course, so the patient will be on the unneeded Zosyn and vancomycin for several days. There are not enough ID docs in the world to approve of antibiotics in real time.

Part of the problem with antibiotics is there are very few side effects to the patient getting antibiotics compared to other drugs, and antibiotics have a certain cache that other drugs lack. My sense is that at the end of life, patients will often opt for antibiotics when they forgo other measures.

The solution? We do not want to make antibiotics more toxic to the patient, so I suggest that every time there is an order for Zosyn and vancomycin (or whatever the decerebrate choice is at your institution), the ordering physician receives a short, painful shock from the keyboard. If you really think the patient needs the antibiotics, you will take the shock. That would likely solve a lot of issues with inappropriate antibiotic use and be simpler than a stewardship program.

See. I am getting too grumpy. But a great idea.

Rationalization

Pharmacotherapy. 2014 Jul;34(7):662–9. doi: 10.1002/phar.1428. Epub 2014 Apr 18. Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime.

http://www.ncbi.nlm.nih.gov/pubmed/24753221

CMAJ. 2007 Oct 9;177(8):877–83. Predictors of inappropriate antibiotic prescribing among primary care physicians.

http://www.ncbi.nlm.nih.gov/pubmed/17923655

Chapter Five

Bare Foot in the Garden

Sep 17, 2014

The patient is a middle-aged male walking barefoot in the backyard when he stepped on a three tined garden claw. It almost went all the way through the foot, tenting the skin on the top. Gives me the willies just thinking about it. The claw had been used for spreading compost in the garden. He had claw removed, the foot cleaned, and was given amoxicillin-clavulanate.

The foot did not get better, and over the next month, it remained painful and draining despite a variety of antibiotics. The top of the foot developed a red bump that was I&D’d. In three days, it was growing an acid-fast bacillus, and the surgeon put the patient on INH and rifampin. Maybe not the best choice.

Three days. I suppose that defines a rapid grower. But which one? I never had an AFB grow quite that fast. And what to do? MRI at least shows no osteomyelitis.

So I picked TMP/sulfa and clarithromycin as best guess pending ID. And it came back several weeks later as Mycobacterium smegmatis. Hmm. Never have seen that one before.

M. smegmatis was first isolated from a syphilitic chancre and, despite the name, has not been isolated from a gentile specimen since 1885. It is found dirt and water and is responsible for mosquito sex change. Yep. Microbiology is weird:

If Mycobacterium smegmatis is around a large body of water, which is where it usually exists, then the bacteria will secrete androstenedione. The androgen in the water causes female mosquito fish to form male anatomical sex organs.

What about soft tissue infections? It caused an infected stifle in a pony. All well and good, but what is a stifle? It’s the joint next above the hock in the hind leg of a quadruped. Somehow I am going to have to work that word into a sentence this week.

There are around two dozen cases of soft tissue infections in the literature, and a chronic draining fistula seems to be a typical manifestation as is the exposure to soil. Debridement, probably to remove dirt, is usually required well as long-term antibiotics and this case is typical:

A history of a soil-contaminated wound should raise the clinical suspicion of infection with this pathogen. Extensive surgical debridement followed by skin grafting has been necessary for the eradication of infection for most patients. Adjunctive antibiotic therapy should be considered and can be chosen on the basis of in vitro sensitivity data.

Treatment is usually doxycycline or a quinolone.

Live long enough, and I suppose I will eventually see one of everything, including a stifle.

Rationalization

Vet Rec. 2000 Oct 14;147(16):452–4. Stifle abscess in a pony associated with Mycobacterium smegmatis.

http://www.ncbi.nlm.nih.gov/pubmed/11079442

Clin Infect Dis. 1993 Apr;16(4):531–3. Soft-tissue infection due to Mycobacterium smegmatis: report of two cases.

http://www.ncbi.nlm.nih.gov/pubmed/8513061

Chapter Six

Angsty Doubt

Sep 19, 2014

I do a lot of driving as part of the job, and it is Audible books that make it enjoyable. Sometimes it even makes me a better driver as I slow down so I can finish a chapter. Most of my 'free' time is spent writing, and if it were not for Audible, I would get very little reading done.

I started a new book today that looked very promising, The Minotaur Takes a Cigarette Break, where the Minotaur is a short-order cook in a Southern restaurant. I loved American Gods and Gods Behaving Badly, also about mythical Gods in the present. During the introduction, it was noted that the author is a professor of English, and I thought, oh crap, the main character is going to be filled with angsty doubt. Ninety minutes in and I moved on to the next book in my cue. Yep. The protagonist is filled with angsty doubt. I'll pass. My day is filled with angsty doubt. I read to escape, not to wallow in more of the same.

The patient is a Hispanic male in his young twenties in the US for a decade. He is treated for fevers as an outpatient with several courses of antibiotics for presumptive UTI, mostly on the basis of fevers and hematuria. He fails to improve and is admitted with a week of progressive shortness of breath and found to be in CHF. The ECHO shows a badly damaged aortic valve.

Endocarditis, right? Blood cultures are negative, but he had been on prior antibiotics. But. As a child, he had been hospitalized for several months for fever and put to bed rest. He had a sore throat for the month before admission, and although he has big tonsils, there is no pharyngitis. His throat culture is negative, but his ASO is markedly elevated. And in the OR, the valve and aortic root are inflamed and indurated, but no vegetation, no pus, no abscess. The pathology shows inflammation, but no organisms.

So. Is this negative culture endocarditis? Can you have endocarditis with no vegetation or pus? Not that I can find. Of course, the vegetation could have come unseated and moved on. Is this acute rheumatic fever? By the Jones Criteria, absolutely.

There are a smattering of valve replacements during acute rheumatic fever, all in patients with aortic valve failure, all from 40 years ago. My case seems similar.

The hematuria could be from ARF:

... four patients with acute rheumatic fever and abnormalities of renal function, urinary sediment, or both have undergone percutaneous renal biopsy at this institution. Distinctly different renal lesions were found and included focal glomerulonephritis, classic acute exudative poststreptococcal glomerulonephritis, mesangioproliferative glomerulonephritis, and severe interstitial nephritis. In each case, the clinical abnormalities were transient.

What to do? There is no one around to ask advice who was alive when ARF was common. Treat for endocarditis (of course, and I may yet get a diagnosis as the valve was sent for molecular testing)? Treat for acute rheumatic fever? He is not symptomatic since the valve was replaced, and I would hate to add aspirin to a patient who has a recent large GI bleed.

Diagnosis and treatment are uncertain. Angsty doubt. I don't need to read about it. It defines my day.

In the end all studies were negative and I treated for acute RF and culture-negative endocarditis.

Rationalization

Br Heart J. Jul 1978; 40(7): 817–819. Aortic valve replacement during acute rheumatic fever.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC483490/

Clin Pediatr (Phila). 1969 Feb;8(2):110-4. Concomitant rheumatic fever and acute glomerulonephritis.

https://doi.org/10.1177/000992286900800212

Ann Intern Med. 1981 Mar;94(3):322-6. Renal lesions in acute rheumatic fever.

http://www.ncbi.nlm.nih.gov/pubmed/7224377

POLL RESULTS

It defines my day:

• Angst 13%
• Doubt 23%
• Schadenfreude 21%
• Inner peace 8%
• 4 of the 7 deadly sins. 33%
• Other Answers 3%
• shoe comfort

Chapter Seven

In Medicine You Can Never Know Enough

Sep 23, 2014

I work hard to keep up with ID. For my Puscast, I skim at least 2000 (yes, that's two thousand) titles a month, download and read about 180, end up discussing around 40. Then there are the references in this blog, and the half-dozen times I search PubMed or Google every day to answer the questions that pop up from consults or curbsides. And it is still not enough. It is never enough.

Case in point.

The patient is immunoincompetent secondary to immunosuppressive medications. She has fevers and upper lobe masses, one cavitary. Percutaneous biopsy and BAL are nondiagnostic. No organisms seen on regular and special stains.

We send off the usual labs, and the only test that comes back is a 1-3 beta-D-glucan of 300. More fungal studies are sent and are all negative, and the lesion gets bigger on voriconazole, the patient is ill, and the 1-3 beta-D-glucan rises to 500. I look over the list of the operative characteristics of the test:

The Fungitell ß-D Glucan assay detects (1,3)- ß-D-glucan from the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, and Pneumocystis jiroveci.

The Fungitell ß-D Glucan assay does not detect certain fungal species such as the genus Cryptococcus, which produces very low levels of (1,3)- ß-D-glucan, nor the Zygomycetes, such as Absidia, Mucor, and Rhizopus, which are not known to produce (1,3)- ß-D-glucan. Studies indicate Blastomyces dermatitidis is usually not detected due to little (1,3)- ß-D-glucan produced in the yeast phase.

With that list, we change to amphotericin B, and still, the lesions enlarge. Then the lab calls me: it is growing an AFB at 2.5 weeks.

Too soon for MTB, and the lab tells me it doesn't look like MTB. Nocardia? No, it is way too acid-fast, Nocardia being weakly acid-fast by Ziehl-Neelsen staining, so probably an atypical mycobacterium.

Do atypical mycobacteria make beta glucans? Not that I can find, but we (we meaning I) treat with INH/Rifampin/Ciprofloxacin/Clarithromycin trying to hedge bets with whatever this rapid grower is. But things are just not right, I can't tie the case into one neat package.

A couple of days later, I get two calls back to back: the lab calls to tell me that it is a Nocardia after all and after I hang up the ER calls to tell me that the patient is in with neurologic symptoms and several ring enhancing lesions on CT.

Ex. Pla. Tive. De. Leted.

Once I had the microbiology, I found it, that one factoid that would have made the diagnosis so much faster, among the 1,265,407 infection articles on PubMed, two case reports. Nocardia makes beta-D-glucan, although I can't find an article on Nocardia cell wall chemistry that proves it.

Subsequently, Nocardia spp. was cultured from the sputum, and pulmonary nocardiosis was established. She gradually recovered after sulfamethoxazole-trimethoprim (ST) administration. The pretreatment serum beta-D-glucan level was highly elevated and decreased in parallel with clinical features.

and

A 78-year-old man administered prednisolone and cyclosporin A for bullous pemphigoid and found in computed tomography (CT) to have a left-lung nodule was suspected of having a fungal infection due to elevated blood (1-->3)-beta-D-glucan. Despite empirical antifungal therapy, however, the nodule grew, followed by new nodules in both lungs. Disseminated nocardiosis was eventually diagnosed based on sputum, blood, and skin cultures growing Nocardia spp.

And now you know too. I wonder what other unknown unknown is out there that will be key to unlocking a case. Of course, I don't know.

Someone needs to do a more systematic evaluation to prove it. There must be a Nocardia maven out there who can do it right. Get on it.

Rationalization

(1–3)-β-D-Glucan Assay: A Review of its Laboratory and Clinical Application

http://labmed.ascpjournals.org/content/42/11/679.full

[Pulmonary nocardiosis with elevation of serum beta-D-glucan in a patient with polymyositis]. Nihon Kokyuki Gakkai Zasshi. 2011 Oct;49(10):750-5. Japanese.

http://www.ncbi.nlm.nih.gov/pubmed/22117312

Kansenshogaku Zasshi. 2009 Sep;83(5):538-43. [A case of disseminated nocardiosis followed by pneumocystis pneumonia in a patient prescribed corticosteroid and cyclosporin A and having elevated blood (1-->3)-beta-D-glucan].

http://www.ncbi.nlm.nih.gov/pubmed/19860256

Chapter Eight

Say Yes to the DRESS

Sep 25, 2014

The bane of my SSI (surgical site infection) existence is P. acnes and summertime. I suppose that should be the banes of my existence.

Summertime always sees a spike in wound infections, especially those that occur 3-4 weeks after surgery and are usually S. aureus. My brilliant idea (as are all my ideas) is to use SMS/Texting to remind patients about proper wound care after discharge. SMS has been effective in getting people to be more compliant with their adherence (or is it adherent with their compliance?) for taking medications. Why not use technology to improve post-operative wound care? It seems an excellent idea to me.

P. acnes is going to be less amenable to amelioration since all we do to prevent wound infections is likely not to work given its protected location in greasy hair follicles.

I had two P. acnes prosthetic valve infections recently. The most recent one presented six months after mitral valve replacement. I presume the organism was acquired at surgery, but maybe not since P. acnes can be found in the blood after dental work.

Not only did the blood and valve cultures grow P. acnes, the valve also had scant enterococcus and a coagulase-negative staphylococcus. One bacteria is bad enough, but three?

Given the sensitivities, I opted for vancomycin, rifampin, ampicillin, and ceftriaxone. I wanted to treat each organism as close to optimally as I could rather than try for a simpler, but perhaps half-assed (as my dad would call it), regimen. As an exercise, I will let you decide which antibiotic(s) for which bug(s).

And then. Two weeks into therapy, she has fevers, pancytopenia, eosinophilia, and an impressive drug rash. DRESS or certainly heading that way. But to which drug? Answer: All of them? The most recent TEE shows no abscess, but there is still myocardial edema. Given the findings at surgery, with multiple abscesses, I want to complete a course of antibiotics.

I am also hesitant to rechallenge with antibiotics as I fret about progression to Stevens-Johnson syndrome, although unusual, DRESS and Stevens-Johnson can overlap.

I opted for daptomycin and clindamycin for the short term while the drug reaction calms down, with the former at 10 mg/kg/d:

Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day...For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success.

Depending on the clinical course and repeat TEE, I may rechallenge her in the future.

Rationalization

Endod Dent Traumatol. 1995 Jun;11(3):142-9. Bacteremia in conjunction with endodontic therapy.

http://www.ncbi.nlm.nih.gov/pubmed/7641631

Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist?

http://www.ojrd.com/content/7/1/72

Antimicrob Agents Chemother. 2006 Aug;50(8):2728-31. In vitro activities of daptomycin, vancomycin, and penicillin against Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes.

http://www.ncbi.nlm.nih.gov/pubmed/16870765

J Antimicrob Chemother. 2013 Dec;68(12):2921-6. doi: 10.1093/jac/dkt294. Epub 2013 Aug 8. A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/23928022

Chapter Nine

Duration Unknown

Duration Unknown

Sep 26, 2014

Life is so strange

Duration unknown

When you don't know

Your Duration

Something could change

It's unknown

And then you won't know

Duration unknown.

Missing Persons

Duration of therapy is a common reason for an ID consultation. It is interesting that after all these years, we so often do not have a clear answer. The real answer is until the infection is cured, but that can be a problematic endpoint to determine.

Except for a few organisms, such as S. aureus and C. albicans which have a nasty predilection for causing metastatic infections, I suspect that the presence of bacteremia has little to do with the duration of therapy as long as the source is controlled:

Twenty-four eligible trials were identified, including one trial focusing exclusively on bacteremia, zero in catheter-related bloodstream infection, three in intra-abdominal infection, six in pyelonephritis, thirteen in pneumonia and one in skin and soft tissue infection. Thirteen studies reported on 227 patients with bacteremia allocated to 'shorter' or 'longer' durations of treatment. Outcome data were available for 155 bacteremic patients: neonatal bacteremia (n = 66); intra-abdominal infection (40); pyelonephritis (9); and pneumonia (40). Among bacteremic patients receiving shorter (5-7 days) versus longer (7-21 days) antibiotic therapy, no significant difference was detected with respect to rates of clinical cure (45/52 versus 47/49, risk ratio 0.88, 95% confidence interval [CI] 0.77-1.01), microbiologic cure (28/28 versus 30/32, risk ratio 1.05, 95% CI 0.91-1.21), and survival (15/17 versus 26/29, risk ratio 0.97, 95% CI 0.76-1.23).

Most organisms in the blood are likely dead shortly after the first dose of antibiotics.

There are also common organisms that show up in blood cultures for which we have no idea what to do.

The patient is an elderly male on daily potassium for a renal wasting syndrome. He has a month of fevers and chills an hour after his nightly IV injections.

Blood cultures are finally drawn, and they all grow coagulase-negative Staphylococcus as does the catheter tip. And the fly in the ointment is a pacemaker for symptomatic bradycardia. How long to treat? Who knows.

The way you give a bunny endocarditis, besides making it a junkie, is to put a wire across a valve and give it a bolus of bacteria. By history, he has had an intermittent bacteremia for a month, so he is a set-up for right-sided endocarditis.

Responsible microorganisms included Staphylococcus aureus in 54.6%, coagulase-negative staphylococci in 37.5%, Candida species (spp.) in 16.6%, and enterococci in 12.5%. Five cases were polymicrobial. The line tip was within the right atrium (RA) in 37.5%, the superior vena cava (SVC)-RA junction in 20.8%, the SVC in 33.3%, and the pulmonary artery in 4.2% of patients. Sites of endocardial involvement were the aortic valve in 6 patients, mitral valve in 7 patients, tricuspid valve in 6 patients, right atrial wall in 11 patients, and pacemaker wire in 2 patients. Isolated right-sided involvement occurred in 50% of cases, isolated left-sided in 33.4%, and bilateral involvement in 16.6%. Transesophageal echocardiography (TEE) was necessary for diagnosis in 10 cases (41.6%).

TEE is pending.

Treatment is easy if there is a vegetation or wire infection: pull the wires and 4 weeks of antibiotics.

But how long to treat if the TEE is negative. I can find no data on the odds that a valve or a pacer will be seeded with a coagulase-negative Staphylococcus bacteremia. Is there any point in a long course of therapy on the off chance the wire is infected, given that the odds of medical cure are tiny? Stop early and see if the bacteremia recurs, simplifying the diagnosis? Or hope I can kill an early infection? It is a run-of-the-mill coagulase-negative Staphylococcus, and I would wager not all coagulase-negative Staphylococci, are the same at causing complications.

Given how common line-related coagulase-negative staphylococcal bacteremia used to be (CLABSI are becoming a thing of the past), we still have no idea how long uncomplicated bacteremia.

The IDSA guidelines say for coagulase-negative Staphylococcal bacteremia

For uncomplicated CRBSI, treat with antibiotics for 5–7 days if the catheter is removed (B-III) ... Alternatively, patients with uncomplicated CRBSI can be observed without antibiotics if they have no intravascular or orthopedic hardware, the catheter is removed, and additional blood cultures (performed on samples collected when the patient is not receiving antibiotics) are obtained after catheter withdrawal to confirm the absence of bacteremia (C-III)

Although they give it a B and C III, the text says

There are no compelling data to support specific recommendations for the duration of therapy for device-related infection.

Writers of guidelines get the privilege of disguising opinion as fact and obscuring the fact with categories of evidence I at least can never remember. Which one is not evidence-based medicine? Oh, yeah, III.

Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

One of the following I suppose:

Basis for clinical decisions	Marker	Measuring device	Unit of measurement
Evidence	Randomized controlled trial	Meta-analysis	Odds ratio
Eminence	Radiance of white hair	Luminometer	Optical density
Vehemence	Level of stridency	Audiometer	Decibels
Eloquence (or elegance)	Smoothness of tongue or nap of suit	Teflometer	Adhesin score
Providence	Level of religious fervour	Sextant to measure angle of genuflection	International units of piety
Diffidence	Level of gloom	Nihilometer	Sighs
Nervousness	Litigation phobia level	Every conceivable test	Bank balance
Confidence*	Bravado	Sweat test	No sweat

And I am fine with that. Someone has to pull all the literature together and come up with the best guess possible with the information available. It is what defines a consultant.

But it sure would be nice to have some real evidence.

Rationalization

Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Critical Care Volume 15 Issue 6.

http://ccforum.com/content/15/6/R267

Clin Cardiol. 2009 Dec;32(12):E48-54. doi: 10.1002/clc.20498. Endocarditis complicating central venous catheter bloodstream infections: a unique form of health care associated endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/20014189

Seven alternatives to evidence based medicine BMJ 1999; 319 doi: http://dx.doi.org/10.1136/bmj.319.7225.1618

http://www.bmj.com/content/319/7225/1618

Chapter Ten

Bad Teeth and Ascites

Sep 29, 2014

Bad teeth and ascites. It sounds like a particularly unpleasant punk duo, perhaps a progenitor of the Sex Pistols, although I quite liked the Sex Pistols back in the day.

Bad teeth and ascites are not a good combination since bacteria from the former can travel to the latter.

The patient has ascites from liver disease and is admitted with fevers and abdominal pain. A paracentesis reveals 400 white cells, and within 24 hours, the ascitic fluid is growing Streptococcus mitis group and Rothia mucilaginosa.

The Streptococcus I knew, but I have not heard of Rothia before. That is due to a name change. I imagine that microbiologists get together every year on some tropical island, sit around a table drinking rum, and changing the names of organisms just to annoy people.

"I know, I know, let's call it Rothia mucilaginosa. Clinicians will think it is a Harry Potter curse," one will say, waving an imaginary wand, and they all break down in drunken laughter.

At varying times it has been known as Staphylococcus salivarius, Micrococcus mucilaginosus and Stomatococcus mucilaginosus, further evidence to suggest that the names of organisms are assigned as part of an alcohol-induced prank.

It is a mouth organism, a gram-positive coccus in clusters, and there are a smattering of diseases in the PubMeds, about 40 cases all told. There are several peritoneal dialysis-related cases but no reported cases of SBP. It responded nicely to ampicillin.

Weirdly, Rothia mucilaginosa shows up in a bit of tooth fairy science. In traditional Chinese medicine (TCM)

TCM determines the appearance of the tongue to be an outer manifestation of the status of the human body. Tongue appearance considers the tongue coating and tongue body. The tongue coating refers to fur-like substances covering the surface of the human tongue, caused by processes of the spleen and stomach. TCM suggests that the tongue coating is a very sensitive index that reflects the physiological and pathological status of the organs, especially the spleen and the stomach.

Tongue appearance is worthless for a real diagnosis since TCM is not based on the reality of anatomy or physiology :

Spleen governing transportation (“Pi Zhu Zhuan Yun” in Chinese) means that the spleen processes substances for transport to nourish the limbs and bones. Phlegm, blood stasis, indigestion, and other pathological factors often cause spleen and stomach disorders. The transpiration of stomach Qi changes the tongue coating, which indicates its possible relationship with abnormal energy circulation.

The words form sentences, but there is no content. And tellingly, no two TCM practitioners can make the same tongue diagnosis.

The findings showed that the TCM tongue inspection for specific characteristics examined was not a reliable diagnostic method, at least for the group of TCM practitioners involved in this study. CONCLUSIONS: The findings suggest that a major contribution to the low levels of inter- and intrapractitioner agreements stems from inadequate operational definitions of both the tongue characteristics studied and of the inspection regions of the tongue.

But that didn't prevent one group from finding that Rothia mucilaginosa has a close correlation with the formation of non-greasy fur on the tongue. I think this may be the first time I have seen a real organism associated with an imaginary physical diagnostic finding. Bacteria show up in the oddest places.

Rationalization

Int J Syst Evol Microbiol. 2000 May;50 Pt 3:1247-51. Characterization of a Rothia-like organism from a mouse: description of Rothia nasimurium sp. nov. and reclassification of Stomatococcus mucilaginosus as Rothia mucilaginosa comb. nov.

http://www.ncbi.nlm.nih.gov/pubmed/10843069

Metabolic markers and microecological characteristics of tongue coating in patients with chronic gastritis.

http://www.biomedcentral.com/1472-6882/13/227

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Oct;32(10):1331-5. [The oral microbial fingerprint on the greasy tongue coating of patients with chronic gastritis].

http://www.ncbi.nlm.nih.gov/pubmed/23163140

Why Traditional Chinese Medicine Diagnosis Is Worthless

http://www.acuwatch.org/reports/diagnosis.shtml

J Altern Complement Med. 2008 Jun;14(5):527-36. doi: 10.1089/acm.2007.0079. Traditional Chinese medicine tongue inspection: an examination of the inter- and intrapractitioner reliability for specific tongue characteristics.

http://www.ncbi.nlm.nih.gov/pubmed/18564955

Chapter Eleven

Erythroderma

Oct 1, 2014

Rules in medicine are almost never 100%. I only know of four that have no exception.*

Cellulitis is never chronic and never bilateral. Never. Ever.

I saw yet another patient in the clinic who had a case of cellulitis (fevers and erythroderma of the leg) that did not go away after multiple courses of antibiotics. I cured it by raising the leg higher than the heart. The redness vanished.

Cellulitis is never chronic and never bilateral. Never. Ever. It is always chronic edema. Except when it isn't.

The patient is a young female who had fevers, rigors, and severe diffuse myalgias for three days before admission with a red, hot, swollen patch on her foot. Eventually, she came to the ER, had a WBC of 25,000 with a left shift, and blood cultures grew S. pyogenes, aka group A Streptococcus. All well and good, and she mostly improved over the next 24 hours, except for the erythroderma did not get better, so they called me.

The physical exam was curious. Not only was there a red patch on the top of the right foot, but there was also one on the top of the left foot and over the elbow. And they were a salmon pink, kind of like a scarlet fever rash. I am lousy at describing a rash, so Google ‘Scarlet fever rash’ if interested.

Is it bilateral or multi-focal cellulitis? Bacteremia does occasionally cause a multi-focal cellulitis, but it is distinctly unusual and more common with Pneumococcus.

And the conjunctiva was very red, but the sclera was spared and the tongue, while not quite a strawberry, was abnormal.

The erythroderma was slow to go away, resolving after the rest of the infection symptoms were gone. Against Scarlet Fever was the rash was not in the classic location, was not rough/sandpaper-like, and did not peel. She never was septic or had MOSF like TSS, and the ferritin was only slightly up, so not Stills.

It is kind of sort of scarlet feverish, or at least partly a Streptococcal toxin-mediated erythroderma more than cellulitis, which is never, ever bilateral. Except when it is.

Rationalization

Eur J Clin Microbiol Infect Dis. 2003 Jun;22(6):337-41. Epub 2003 Jun 3. Bacteremic pneumococcal cellulitis compared with bacteremic cellulitis caused by Staphylococcus aureus and Streptococcus pyogenes.

http://www.ncbi.nlm.nih.gov/pubmed/12783279

Q J Med. 1988 Nov;69(259):921-5. Septic scarlet fever due to Streptococcus pyogenes cellulitis.

http://www.ncbi.nlm.nih.gov/pubmed/3078213

*In case you were curious and/or a new reader:

\1) The infection goes to disc space, and tumor spares the disc.

\2) Use of 'strong,' 'big gun,' or 'powerful' to describe an antibiotic mark the speaker as an idiot about ID.

\3) When applied to choosing a therapy, the three most dangerous words in medicine, never to be trusted, are 'In my experience.'

\4) Anyone who wears their scrubs to the store is an ass who really wants a 'Look at me. I'm a doctor' sign.

I have yet to see an exception to any of the above.

Chapter Twelve

Bowel to Aorta or Aorta to Bowel?

Oct 3, 2014

This is the 7th year of this blog, having started September 7, 2008. It still amazes me that I can write an entry 2 or 3 times a week and have probably well over 1000 blog entries. I have yet to run out of material or repeat myself (that would be the clinical material, not the 'humor'). Every day I wonder what I am going to discuss, and it is rare that the universe doesn't serve up an ID curiosity to ramble on about. ID is amazing that way.

The patient is an elderly male with the usual medical problems of modernity: hypertension, type II diabetes, former smoker, obesity who had an abdominal aneurysm repaired with an endovascular stent.

He initially does well, but a month later has progressive abdominal/back pain that slowly worsened over several months, getting acutely worse 24 hours before admission.

A CT showed a duodenal perforation into and around the aortic aneurysm and graft and so off to the OR for a repair. The op note is worth reading for the observations of the surgeon, an experienced, and I would say, wise doctor:

I could see the endovascular graft in place in the abdominal aortic aneurysm and it was over an inch to an inch and a half away from the duodenum, and there was no bile staining of the graft itself. I did not find any pus that I could identify as such within the abdominal aortic sac or in the retroperitoneum. The reaction was inflammatory in this area... This made me wonder if it could be that the aneurysm had been infected... I would theorize that the aneurysm had been eroding in some inflammatory nature prior to its exclusion with endovascular graft and that the procedure itself did not lead to this complication but rather kept the patient from bleeding when the erosion eventually occurred which was likely just in the few days prior to admission.

And Bingo was his name-oh. The cultures support that hypothesis: it was an aneurysm infection that eroded into the duodenum. It grew? Clostridium septicum.

There are several dozen cases of C. septicum causing infection of the aorta, often in association with bowel cancer, which the patient does not have, although colonoscopy has yet to be done. There is one reported case of a C. septicum infection of the aorta after stent placement. While my first aneurysm infection with this organism, it has not been an uncommon pathogen in my practice, seeing a case every couple of years.

It is usually a fatal disease, although my patient is doing quite well. The plan will be lifelong antibiotics.

Rationalization

J Mal Vasc. 2011 Dec;36(6):355-63. doi: 10.1016/j.jmv.2011.08.002. Epub 2011 Oct 19. [Mycotic aortic aneurysm infected by Clostridium septicum: a case report and review of the literature].

http://www.ncbi.nlm.nih.gov/pubmed/22014579

Vascular. 2012 Apr;20(2):104-6. doi: 10.1258/vasc.2010.cr0245. Epub 2011 Jun 29. Clostridium septicum post-endovascular aneurysm repair stent-graft infection.

http://www.ncbi.nlm.nih.gov/pubmed/21715552

Classical Gas. Gangrene.

http://boards.medscape.com/forums/?128@@.29ff634d!comment=1

Chapter Thirteen

Ebola-Smacked

Oct 16, 2014

There is a British term gob smacked. I am adding a new term to the lexicon: Ebola-smacked. You will see why. Since getting back from ID Weak, I have been spending a lot of time preparing for a potential Ebola case. I think that it is unlikely that we will see a case of Ebola here in Portland, the backwaters of the Pacific Northwest, since there are no direct flights from Africa. Still, we have to be ready, so many meetings going through protocols and making sure we are prepared. We don't want to be caught with our hazmat down.

Then at 9:30 a.m. came the call. There was a flight landing at noon, with one or more people from an Ebola endemic area with potential Ebola symptoms, and they might be coming to one of my hospitals.

The next couple of hours were busy as we prepared the ER for potential Ebola cases. It was remarkable how quickly chaos became organized, how everyone came together to solve one issue after another: where were the patients going to go, how to handle family and potentially contaminated clothing, how to draw and test blood, and above all making sure that PPE was correct and maximally protected out staff.

I suspect after what I learned at ID Weak and from what I can infer from the reports out of Dallas (and I wish we had more specific information) is that the infectivity of Ebola during the hemorrhagic stage, when patients make liters of infected material a day in the ICU, was underestimated. Unfortunately, the response to new situations often requires several iterations of trial and error before we figure out the optimal approach, and Dallas was on the wrong end of the learning curve. It is the nature of the beast.

Fifteen minutes before the plane landed, we met in a room, and everyone went through the plan and their roles. I lack the language to describe the professionalism displayed by my colleagues. Everyone was ready to go. We were going to hit the beach.

Then we got the call from the Health Department who met the plane: false alarm. No Ebola. So back to work, although I was remarkably fatigued for the rest of the day. I must have had more of an adrenaline surge than I was aware of at the time.

I am glad we had a false alarm. It showed where there might be potential issues and accelerated our planning for Ebola. Although it is still extremely unlikely that we will see an Ebola case, I am confident we will be able to care for patients and protect our workers.

One of the issues on the agenda for later in the week was how, as a system, are we are going to handle an Ebola patient. Perhaps a single hospital with a dedicated team and, if so, which hospital. As long as all the key people were in the ER for the false alarm, we started that discussion.

For background, our system has one of two children's hospitals in Portland, but it is physically separated from the adult hospitals. That leads to potential logistical problems with staff and equipment if we have to care for both an adult and child case at the same time.

As we brainstormed the options, someone suggested that if we had both an adult and child case, mother and child, perhaps we could take the adult and transfer the child to the other children's hospital in the city. One of our nurses replied simply, "I would just as soon take care of the child. It is what we do."

No one disagreed.

It is what we do. And I am very proud and lucky to work with these people.

Chapter Fourteen

What's Going On?

Oct 17, 2014

The patient is an elderly female who, as part of a unilateral deafness evaluation, had syphilis serology. It was kind of positive: 2 plus FTA but a negative RPR.

History, you ask?

One lifetime male partner, his serology is negative.

She has had but one infection in her life and has never, to her knowledge, had a course of antibiotics.

Five children, all healthy.

She is from rural Columbia and has lived in the US for a decade. At age 2 she had a febrile illness with a rash on her leg that lasted a week and improved on its own, although the provenance of that bit of history is, of course, suspect.

The exam is totally negative.

All the labs are negative, including HIV.

So what's going on?

Treated syphilis? The patient was told she probably got syphilis from her parents, but that seems unlikely to me.

"Burned out" syphilis?

Positive T. pallidum specific serology, low or negative RPR - stable pattern on repeat testing with or without treatment. Clinically asymptomatic.

Prozone effect?

Our results showed that the incidence of the prozone phenomenon was low (0.83%) and could occur during any clinical phase, particularly during primary and secondary syphilis. Pregnancy and neurosyphilis were associated with the prozone phenomenon; sex, age, and whether the patient had been treated were not. The results also revealed that the prozone phenomenon not only occurred in patients with a high titer but also could occur in patients with a moderate/low titer. In fact, almost 31% of the patients with the prozone phenomenon had titers ≤1:16.

Yaws? It was endemic in her part of the world growing up, and perhaps that was the illness at age two.

When I was a kid, there was a burger joint in NE Portland with particularly good burgers and fries, at least as I remember it. It was called Yaws. Now I wonder just what was in the burger.

And finally, a false positive test.

The Hemagglutination Treponemal Test for Syphilis gave the lowest overall percentage of false-positive reactions (1.6%), followed by the Fluorescent Treponemal Antibody-Absorbed test (3.3%) and the Rapid Plasma Regain-Card test (10.8%).

So which is it? No idea.

Syphilis and TB remain the two common infections that remain difficult to diagnose with assurance. So I have to go with the worst case. So will get an LP (I bet it will be negative) and treat for either late latent or neurosyphilis depending on the results.

Postscript

After much deliberation, the patient declined an LP and went with treatment for late latent.

Rationalization

J Infect Dis. 1977 Oct;136(4):548-54. Yaws in the Americas, 1950-1975.

http://www.ncbi.nlm.nih.gov/pubmed/908852

Trans R Soc Trop Med Hyg. Oct 2014; 108(10): 601–607. Endemic treponemal diseases

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162659/

Clin Infect Dis. 2014 Aug;59(3):384-9. doi: 10.1093/cid/ciu325. Epub 2014 May 6. Incidence and risk factors for the prozone phenomenon in serologic testing for syphilis in a large cohort.

http://www.ncbi.nlm.nih.gov/pubmed/24803377

False-positive reactions in the rapid plasma reagin-card, fluorescent treponemal antibody-absorbed, and hemagglutination treponemal syphilis serology tests.

http://jcm.asm.org/content/9/3/369.short

Chapter Fifteen

Mazel tov

Oct 21, 2014

Thanks to technology, I get to know the names of bacteria more often. And if you read fantasy, you are aware that once the true name of something is known, you have total power over it.

The patient has a known bicuspid aortic valve and comes in with fevers and night sweats followed by progressive shortness of breath. All his blood cultures are positive, the ECHO shows a vegetation, and after stabilization with a few days of antibiotics, his valve is replaced.

Everything, including the vegetation, grows Staphylococcus warneri, a coagulase-negative Staphylococcus.

This organism causes mostly prosthetic valve endocarditis with one case of native valve in the literature. It crops up as a cause of other prosthetic infections and it is also occasionally found in ready to eat fish products, including trout, and on nurse's pens. He has no exposure to trout or pens.

He did quite well clinically, but what is also cool is how fast the organism was given a name.

Any sufficiently advanced technology is indistinguishable from magic. Arthur C. Clarke.

We now have a Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass-spectrometer for the identification of bacteria, and I watched it in use last week. They put a touch of bacteria on a slide, zap it with a laser and evaluate the results to give me the name of the bug, all in a machine the size of a refrigerator.

Amazing. Magic, I think. ID docs, or at least this ID doc, really like to know the name of the bug. Saying Alpha Streptococcus or coagulase-negative Staphylococcus is just unsatisfying. ID is finally getting out of the era of stone knives and bearskins and agar plates and into modernity.

Rationalization

J Clin Microbiol. 1992 Feb;30(2):261-4. Clinical significance of Staphylococcus warneri bacteremia.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC265043/

Rapid identification of staphylococci from prosthetic joint infections using MALDI-TOF mass-spectrometry.

http://europepmc.org/abstract/med/20963723

Lett Appl Microbiol. 2014 Nov;59(5):500-6. doi: 10.1111/lam.12304. Epub 2014 Jul 25. Isolation of methicillin-resistant Staphylococcus spp. from ready-to-eat fish products.

http://www.ncbi.nlm.nih.gov/pubmed/25059796

Vet Microbiol. 2014 Feb 21;169(1-2):80-8. doi: 10.1016/j.vetmic.2013.12.012. Epub 2013 Dec 25. Staphylococcus warneri, a resident skin commensal of rainbow trout (Oncorhynchus mykiss) with pathobiont characteristics.

http://www.ncbi.nlm.nih.gov/pubmed/24438987

Iran J Nurs Midwifery Res. 2014 May;19(3):331-3. Do the pens used by nursing students in clinics cause bacterial contamination?

http://www.ncbi.nlm.nih.gov/pubmed/24949075

POLL RESULTS

Medical technology

• is easily understandable 12%
• magic 16%
• gibberish. 2%
• they are just making up words on the fly 22%
• cool even if I do not understand any of it. 45%
• Other Answers 4%
  • is one of the best jokes we've played on MDs yet.
  • was an interesting, challenging, rewarding career, until hospital/lab politics turned it into a spirit-sucking job with a black future.

Chapter Sixteen

Look. But Do Not Touch.

Oct 22, 2014

When I was a medical student in the early '80s (1980s, BTW. I'm not that old), a dermatologist at my medical school enthusiastically encouraged us to touch rashes.

Feel them, she should say, get a sense of them. You can learn a lot by how a rash feels.

She was evidently not trained in ID, and this was long before we worried about blood and body fluid exposures.

Fast forward to my first year in practice, back in 1990. A patient was admitted with fevers and diffuse erythroderma, and many of the house staff saw her rash and touched it. The next day the VDRL came back positive.

NEVER touch a rash of you do not know what it is.

Several of the residents opted for a benzathine penicillin shot rather than have some 'splaining to do with their spouse.

How infectious is secondary syphilis? All the texts say very, but I cannot find a study looking back as far as the 1840s that quantifies just how infectious it is.

In 1865 it was noted that

we are far from being unanimous as regards of the possibility of the transmission of secondary or constitutional syphilis.

I am sure the reference is out there, but it is buried in many other interesting but not quite relevant studies of lues.

So when the patient is admitted with fevers and a rash, including the palms and soles, I know not to touch the skin. I have the advantage of knowing that her VDRL was negative 6 months ago, and now is 1:64.

Part of the problem is she became quite ill after the IM penicillin, and it was a concern that it was an allergic reaction. However, I suspect it is all a Jarisch-Herxheimer reaction, which occurs in about 10% of patients after penicillin.

What I did not know was that the Jarisch-Herxheimer reaction also would occur after mercury, bismuth, and arsenic in the pre-antibiotic days.

A not uncommon disease with common manifestations from both the diseases and the treatment.

I have to be careful with this disease. Not only is it potentially transmissible by touch, but it can lead to endless time spent reading old accounts on the web of a disease that at one time caused tremendous morbidity and mortality but now is easily cured.

After this was published, one of my readers pointed me to How infectious is syphilis?

In a study of the sexual contacts of patients with primary and secondary syphilis, 65 of 127 (51%) contacts at risk developed syphilis. There was no significant difference between figures for homosexuals (48/98, 49%) and for heterosexuals (17/29, 58%). Our findings are similar to those of the prepenicillin era, but the question. Why are so few contacts infected? Remains unanswered.

58% seems like a lot to me.

Rationalization

Note the dates on some of the references. Worth a click

Clin Microbiol Rev. Jan 2005; 18(1): 205–216. Secondary Syphilitic Lesions

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC544174/

Br Med J. Feb 4, 1865; 1(214): 111–112. Case of Transmission of Secondary Syphilis: With Remarks

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2325418/

J Natl Med Assoc. 1929 Apr-Jun; 21(2): 39–42. Secondary Syphilis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2624831/

Med Chir Trans. 1860; 43: 57–70.1. On a Form of Secondary Syphilitic Inoculation

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147769/?page=1

JARISCH-HERXHEIMER REACTION IN EARLY SYPHILIS THOMAS W. FARMER, M.D. JAMA. 1948;138(7):480-485. doi:10.1001/jama.1948.02900070012003.

http://jama.jamanetwork.com/article.aspx?articleid=301808

Br J Vener Dis. 1983 Aug; 59(4): 217–219. doi: 10.1136/sti.59.4.217

How infectious is syphilis?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1046186/

Chapter Seventeen

Lots of Back Pain

Oct 24, 2014

Back pain is not a large part of my practice. Except.

There is, of course, the IVDA who presents with fevers and severe back pain. I had a pair of these this week. Both had MRI's that showed discitis with the adjacent endplates involved. It is always infection with that MRI pattern, probably one of only four things in medicine that are 100% always true. Both had MRSA in the blood, so the diagnosis was not in doubt.

The issue with these patients is not what to do but how to deliver the appropriate therapy. Lack of insurance, homelessness, drug addiction, and mental illness all make for difficult delivery of appropriate MRSA therapy. But that is medicine in the US. I have yet to have to compromise therapy on my end due to any of the above, although on occasion, the patients do not follow up.

The other form of back pain is a more indolent but progressive back pain in otherwise normal people. Some minor trauma, lifting or falling, that leads to a back twinge that over the following weeks has increasing back pain. Eventually, an MRI is done that has the same, diagnostic, findings.

I had a pair of these this week as well. One was an MSSA, and one was culture negative. These cases tend to be less about how to deliver the therapy and more about the cause. I presume that the trauma led to bleeding, and then the clot was seeded from the bacteremia that is part of life. When the initial trauma occurs at work, it becomes a workman's comp issue.

My suspicion is that I am seeing more of this in older patients, so I suppose having an old spine doesn't help:

Spinal infection is a rare, but possibly increasing, cause. We describe a retrospective case note review of 41 patients aged 65 years and over with spontaneous spinal infections over a 6-year period. The incidence was 9.8/100,000/year. Staphylococcus aureus was the most common isolate. The mean time from symptom onset to diagnosis was 34 days. Most patients presented with back pain and elevated CRP.

The problem, of course, is differentiating the occasional infection from the all too common musculoskeletal back pain without getting MRIs on everyone.

I wonder if the hint is in the history: the relatively slow onset of progressively severe pain after trauma rather than the more sudden onset of non-progressive pain that occurs with musculoskeletal trauma and acutely herniated discs. If that is the hint, I can't find a reference in the PubMeds, but it sure seems to be the case.

Rationalization

Neurosurg Focus. 2014 Aug;37(2):E3. doi: 10.3171/2014.6.FOCUS14148. Diagnosis and management of primary pyogenic spinal infections in intravenous recreational drug users

http://www.ncbi.nlm.nih.gov/pubmed/25081963

Intern Med J. 2009 Dec;39(12):845-8. doi: 10.1111/j.1445-5994.2009.02052.x. Spontaneous spinal infections in older people.

http://www.ncbi.nlm.nih.gov/pubmed/20233246

Journey or Destination

Oct 27, 2014

They say it is the journey that is important, not the destination. I suppose that is true if you are Steve Perry. Both are important in medicine. How you get to the diagnosis can be as interesting as the final diagnosis, but there is little in life as satisfying as coming up with an unusual diagnosis and being proven right. Most of the time, the unusual diagnosis does not pan out, but for all you youngsters starting out in practice, people will always remember the great call and forget all the misses.

For today there is the journey.

The consult is an elderly female with a hematogenous malignancy in remission who develops a fever three weeks into a trip to China. No diagnosis is made in China, the fevers remit for a day, and she returns home only to have the fever return. So off for admission to the hospital.

She has no good ID exposures on the trip, and no one else was ill. The exam is negative, and routine labs show the baseline pancytopenia is a little worse. The patient is totally wasted by the illness, not even wanting to lift her head off the pillow. There is one feature upon which I am going to hang my clinical diagnosis.

Her temperature is 104.5, but the pulse is only 90. Faget's sign, which I learned a minute ago, is also called sphygmothermic dissociation. Cool. I like obscure and archaic words. Sphygmothermic dissociation has a narrow differential, the big three being Typhoid fever, Brucellosis, and Yellow fever.

A quick Google shows that Typhoid fever is a big problem in China at the moment from both S. typhi and S. paratyphi, and there is increasing quinolone resistance.

I called the CDC today and talked it over with the powers that be, curious if there was more up-to-date information on resistance while waiting on cultures. They confirmed the resistance to quinolones. People have been a wee bit critical of the CDC of late, but having had to deal with small-scale outbreaks over the years, I know how hard it can be to know what to do with new problems. It is difficult enough to know what to do in my ICU, much less the whole country. I feel sympathy for all those in public health given all the Dunning-Kruger armchair quarterbacks second-guessing their decisions. Recently someone asked in the comments if I still had confidence in the CDC. Yep. Sure do. And as soon as you are perfect, be sure to run for God.

In the meantime, it is ceftriaxone and wait on cultures and serology. If I reach the destination of Typhoid fever, I will let you know.

Postscript

It wasn't.

Rationalization

Zhonghua Liu Xing Bing Xue Za Zhi. 2013 Mar;34(3):254-8. [Fever monitoring program in areas with high incidence of typhoid and paratyphoid fever in Guizhou province].

http://www.ncbi.nlm.nih.gov/pubmed/23759232

Bull World Health Organ. 2010 Sep 1;88(9):689-96. doi: 10.2471/BLT.09.069310. Epub 2010 Apr 7. Trends and disease burden of enteric fever in Guangxi province, China, 1994-2004.

http://www.ncbi.nlm.nih.gov/pubmed/20865074

Antimicrob Agents Chemother. 2007 Dec;51(12):4315-23. Epub 2007 Oct 1. Antimicrobial drug resistance of Salmonella enterica serovar typhi in Asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.

https://doi.org/10.1128/aac.00294-07

Why is typhoid fever a problem in China?

https://microbewiki.kenyon.edu/index.php/Typhoid\_fever\_in\_ChinaWhy\_is\_typhoid\_fever\_a\_problem\_in\_China.3F

Demi-Buttock

Nov 3, 2014

We all bring biases to the table. When I was a kid, if my chores were not done to the satisfaction of my father, he referred to the work as 'half-assed.' It has since been my goal to be full-assed in all my work. While I will argue that there is no such thing as 'strong,' 'big gun,' or 'powerful' antibiotics, I do think there are half-assed antibiotics.

The patient has a femoral pseudoaneurysm from injection drug use that ruptures. It happens. I am reminded of one of my fellow interns (not me. really) who could not get blood out of an IVDA, and the patient grabbed the syringe from him and stuck her femoral vein to get the sample. Boy, did he get chewed out for that.

The aneurysm is repaired and is grossly infected in the OR. The patient is put on vancomycin and piperacillin/tazobactam, for me, the archetype of half-assed antibiotics. But then, isn't everyone put on that combination these days? Yep.

Of 7641 drugs to treat infections, the most common were parenteral vancomycin (1103, 14.4%; 95% CI, 13.7%15.2%), ceftriaxone (825, 10.8%; 95% CI, 10.1%11.5%), piperacillin/tazobactam (788, 10.3%; 95% CI, 9.6%11.0%), and levofloxacin (694, 9.1%; 95% CI, 8.5%9.7%).

Vancomycin, while half-assed, I can understand, given the ubiquity of MRSA. All our antibiotics for MRSA are half-assed. But piperacillin/tazobactam? This drug has become extremely popular in the last decade, and I do not know why. I assume great drug detailing. I do not think I have ever ordered piperacillin/tazobactam.

It is because I have this other bias. If bug 'x' was on my mother's prosthetic aortic valve and she was not a surgical candidate, what would 'x' have to be so I would use piperacillin/tazobactam (assuming no odd resistance pattern that would force my hand)? I cannot think of one. So why use it for any other infection?

I like to kill my bacteria directly and fret about the diversity of beta-lactamases, not all of which are inhibited by tazobactam.

Multidrug resistance has been increasing among Gram-negative bacteria and is strongly associated with the production of both chromosomal- and plasmid-encoded beta-lactamases, whose number now exceeds 890.

That is a competition we are never going to win.

Most antibiotics work just fine in most patients most of the time as long as you have good source control, so half-assed antibiotics will usually suffice. But when I see them used, I hear the voice of my father and see that shake of the head and roll of the eyes, especially when they are used in lieu of better, less expensive, antibiotics.

The cultures grew MSSA and S. pyogenes and, as is often the case, the antibiotics are continued despite the culture results, at least until the ID consult late into the hospitalization.

Surgeons typically ignore culture data after an operation, and only 8.8% of patients in this study had an appropriate change in antibiotic treatment after the operation. A benefit from obtaining operative cultures could not be identified.

I guess an appropriate change is not considered a benefit.

I can hear my dad now.

Rationalization

Centralize Chir. 2004 Jan;129(1):21-8. [Analysis of vascular complications in intra-venous drug addicts after puncture of femoral vessels].

http://www.ncbi.nlm.nih.gov/pubmed/15011108

JAMA. 2014 Oct 8;312(14):143846. doi: 10.1001/jama.2014.12923. Prevalence of antimicrobial use in US acute care hospitals, May September 2011.

http://www.ncbi.nlm.nih.gov/pubmed/25291579

Clin Infect Dis. 2008 Mar 15;46(6):862-7. doi: 10.1086/528712. Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint.

http://www.ncbi.nlm.nih.gov/pubmed/18279040

The New β-Lactamases http://www.nejm.org/doi/full/10.1056/NEJMra041359

Crit Care. 2010;14(3):224. doi: 10.1186/cc8892. Epub 2010 Jun 29. Bench-to-bedside review: The role of beta-lactamases in antibiotic-resistant Gram-negative infections.

http://www.ncbi.nlm.nih.gov/pubmed/20594363

Antimicrob Agents Chemother. 1993 Oct;37(10):2059-63. Characterization of a new TEM-type beta-lactamase resistant to clavulanate, sulbactam, and tazobactam in a clinical isolate of Escherichia coli.

http://www.ncbi.nlm.nih.gov/pubmed/?term=8257123

Ann Surg. Nov 1991; 214(5): 543–549. Antibiotic treatment for surgical peritonitis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358607/

POLL RESULTS

I

get cultures and change antibiotics accordingly. 62%

get cultures and let the ID doc deal with the result. 17%

get cultures and forget about them. 0%

don't get cultures. Vancomycin and pip-tazo kills everything. The rep told me so over steak. 5%

decide on the whim of the moment whether to culture, then start some big gun, broad-spectrum antibiotic 10%

Other Answers 5%

give no antibiotics

self-medicate, then nap PRN.

I do not treat patients anymore

Chapter Twenty

Style

Nov 6, 2014

I sometimes think being a specialist means being ignorant with style. All too often, I am asked to weigh in on a case about which I know nothing and, after a review of the literature, I am none the wiser. So I reason as best I can with the information I have and provide an answer. Not the right answer, perhaps, but an answer.

A case in point.

The patient is a middle-aged male with ascites of uncertain etiology. He does drink, but not a lot, and his transaminases are mostly normal. He has an extensive work by his gastroenterologist that is mostly negative except for the liver biopsy: cirrhosis and inflammation, consistent with a viral hepatitis, mostly favoring CMV. So the patient is sent off to see me.

And?

Got me.

The patient has no symptoms that suggest either CMV or hepatitis. The CMV viral load is negative in the blood, and the IgM is negative, with a very high IgG.

Hepatitis can be due to CMV in normal people and can be part of any acute CMV infection. So hepatitis is not that odd due to acute CMV. But serologically, this is not an acute infection but a reactivation. All the reactivation hepatitis occurs in patients with one immunodeficiency or another, and my patients are immunologically normal.

I can find no evidence that CMV has ever been associated with either reactivation hepatitis or cirrhosis in normal hosts. I asked an older, and therefore wiser, gastroenterologist is they had ever seen CMV on a liver biopsy in a similar situation. Nope.

This is not the first time I have had CMV discovered serendipitously on a biopsy. I suspect the occasional reactivation under stress is not that uncommon and, most of the time, not clinically importantly, at least to judge from symptoms and CMV viral load.

My final data-free conclusion? Probably real, perhaps reactivation due to the stress of whatever is going on in the liver, and neither clinically important nor requiring treatment. But I said it with style.

Rationalization

Am J Case Rep. 2014 Oct 18;15:447-9. doi: 10.12659/AJCR.890945. Cytomegalovirus-induced hepatitis in an immunocompetent patient.

http://www.ncbi.nlm.nih.gov/pubmed/25325934

POLL RESULTS

I cover my ignorance

• with style 13%
• a blizzard of BS 13%
• a withering style 2%
• by hiding the restroom 13%
• a broad smile; it is bliss after all 49%
  • Other Answers 9%
  • Socrates
  • By standing next to Senator Inhofe.
  • defer to other specialists
  • in the old days, as just another MMMM.(mumbling male med tech) Thanks, Sandy.

Chapter Twenty-One

Flaccid

Nov 10, 2014

The patient went to bed, feeling fine. When she awoke in the morning, she could not move her right arm. She waited a day to see if it would improve (no insurance). It did not, so off to the ER.

She has no past medical history or exposures of note. She was not intoxicated and did not sleep in a 'funny' position.

Exam shows no sensory problems, and she can ever so barely move her index finger. There is a rash. One rash is across the upper arm like a band covering 3/4's of the circumference and about half an inch across. The ring finger has a vesicular rash on the top. I count at least three dermatomes involved.

Labs are negative, and the MRI shows inflammation of the brachial plexus.

Zoster leads the list with rash:

The mean age of onset was 71 years, 67% were men, and the lower limb was affected in 55%. The mean weakness score was 2.0 (0 = normal strength, 4 = plegia). Most patients developed postherpetic neuralgia (PHN, 92% at 1 month and 65% at 3 months), and the average minimum duration of weakness was 193 days. ZALP was caused by radiculopathy (37%), plexopathy (41%), mononeuropathy (14%), and radiculoplexus neuropathy (8%). MRI demonstrated nerve enlargement, T2 signal prolongation, or enhancement in a majority (64%) of affected plexi and peripheral nerves. CONCLUSIONS: ZALP is associated with considerable weakness. It typically lasts at least several months, localizes to plexusor peripheral nerve in 63%, and is associated with high rates of PHN.

and she fit the clinical pattern nicely. It would be nice to have some pain, only one dermatome involved, and it is most annoying that the cultures/studies of the rash failed to find VZV.

I wondered about enterovirus D68, which can cause paralysis in just the arms, but she has no exposure to children. No other infection (VDRL negative), physiologic, or anatomical reason was found for the plexopathy, including a lightning strike, so we treated her for VZV despite the negative cultures. At the time of discharge, motor function was returning.

So I am calling it a varicella-sister brachial plexopathy. Close enough for ID work, but far enough to be unsatisfactory.

Rationalization

Muscle Nerve. 2014 Aug;50(2):177-85. doi: 10.1002/mus.24141. Epub 2014 May 14. Clinical, electrophysiologic, and imaging features of sister-associated limb paresis.

http://www.ncbi.nlm.nih.gov/pubmed/24638224

Paralysis in Children With Enterovirus D68

http://www.medscape.com/viewarticle/832556

J Neurosci Rural Pract. 2014 Oct;5(4):399-400. doi: 10.4103/0976-3147.140000. Lightning strike-induced brachial plexopathy.

http://www.ncbi.nlm.nih.gov/pubmed/25288846

Chapter Twenty-Two

Clinical Call

Nov 14, 2014

I am often called upon to weigh in on complex cases with no clear answer.

A typical case is an ICU patient with MOSF, intermittent fevers, a leukocytosis all for no good reason. The what and why of admission is rarely relevant as they are now deep into their hospital stay. All the cultures are negative except for a scant Candida here or a low amount of normal flora there. All the scans are unrevealing, the patient remains on the ventilator and is on vancomycin and some anti-pseudomonal beta-lactam or other.

The way I figure it, if there is not a pocket of pus somewhere on scans and the cultures are negative for MRSA or Pseudomonas, there is no need to continue the antibiotics.

Most bacterial infections are infections of something. Some organ has to be involved, and the bloodstream is an organ. And if you do not grow MRSA or Pseudomonas, those bugs are not there.

I had a case just this week. We worked them up, found nothing, and I said you could stop the antibiotics. The patient has no infection that is being treated by the current antibiotics.

Of course, the other doctors involved in the case were hesitant to follow my advice. I knew they would be. The patient is ill, the diagnosis is uncertain, and most do not have my arrogance, urm, I mean experience for making clinical decisions.

We do not offer the procalcitonin in my institutions as I have never figured out when to use it, given its sensitivity and specificity, maybe 90% for both. Perhaps it is like the troponin. I am too old and set in my ways to know what to do with the result. One doc in another hospital system told me he could not round in the ICU without it. I seem to do just fine.

There is one hospital I go to where many of the hospitalists were trained were the procalcitonin is common, and they seem to order it willy-nilly, often for cases that are high probability for serious bacterial infections.

As was pointed out in this fine website, Procalcitonin Testing Is No Use Without Clinician Education:

The use of a procalcitonin (PCT) test to guide antibiotic therapy in patients with lower respiratory tract infections and sepsis is of no value without education on how to interpret the results, a new study suggests. "Providers were ordering the PCT test, but did not know how to interpret the test result,"

So maybe I just need more edumacation.

As a tie-breaker, we sent off a procalcitonin, and while we waited for results, the antibiotics were stopped. And it came back at 0.4 ng/ml, which, as I read the interpretation guide, makes pneumonia unlikely, sepsis possible, and is too high to stop antibiotics.

In the 72 hours it took for the results to come back, the patient continued to do improve off antibiotics.

So did I learn anything? Yeah. Probably should not have bothered with the procalcitonin and relied on my arrogance, er, clinical acumen.

Rationalization

There are so many reviews and studies about procalcitonin that I'll let you cherry-pick the one you prefer to support its use or lack thereof.

POLL RESULTS

Concerning the procalcitonin

• I can't round without it. 1%
• I never use it 25%
• I can't figure out an ESR, much less the procalcitonin 4%
• I use it on select cases along with the C Re-Active Protein (CRAP) 46%
• We can't afford it, use the amateur-calcitonin instead. 19
• Other Answers 4%
  • I can round without it. I occasionally use it as a tool for a beginner to learn its clinical meaning. The result: as ESR and CRP.
  • never heard of it
  • It is a nice stick in my antimicrobial stewardship arsenal

Chapter Twenty-Three

Words Fail

Nov 17, 2014

A picture may be worth a thousand words, but no amount of words will ever adequately describe a picture, especially if it is from the Radiology department.

I was asked to see a patient with a complex abdominal history: cancer, radiation, fistula, gallbladder removal, shunts, stents, hysterectomy, pancreatitis, and colectomy all in the last year.

After the most recent surgery (cholecystectomy, lysis of adhesions), the white cell count was up, and the CT showed numerous fluid collections in the abdomen.

I read the report and compared it to the picture. Got me. The most worrisome collection was in the gallbladder fossa: what looked to me to be air-filled infected phlegmon, but there were a variety of other collections that did not look worrisome to my eye. The report was noncommittal.

So I did the diagnostic test that most people seem to avoid now that the X-rays can be pulled up on the computer. I walked down to radiology to review the films with the radiologist.

It seems passé these days, but one of my many rules in medicine is to go over any abnormal studies with radiology and not to rely on the report. I have learned a tonne (so much it is the English measurement) over the years by doing so and have become a better reader of X-rays as a result.

I was not disappointed. The radiologist agreed with my take on the fluid collections (seroma here, hematoma there) save one. What I thought was an air-filled infected phlegmon she said was just packing.

I did not know packing could look like an abscess, so I called the surgeon, and he said yep, the gallbladder fossa had refractory blood oozing, so he stuffed the area with packing. Or packed the area with stuffing. Anyway, there is absorbable surgical stuff in there.

Gelatin absorbable sponge may mimic a postoperative abscess on CT. Findings that may help differentiate the hemostatic agent from abscess include linear arrangement of tightly packed gas bubbles, fixed position of gas bubbles on subsequent examinations, shape, lack of air-fluid level, and lack of enhancing wall.

And that was the phlegmon. It was not mentioned in the report because the radiologist who read the film did not have the benefit of conversing with a treating physician asking a bunch of questions: what's that? And that? And how about that?

Never rely on the report, look at the films with the radiologists.

Rationalization

AJR Am J Roentgenol. 2005 Feb;184(2):475-80. Distinguishing gelatin bioabsorbable sponge and postoperative abdominal abscess on CT.

http://www.ncbi.nlm.nih.gov/pubmed/15671366

Chapter Twenty-Four

Consider The Heel

Nov 19, 2014

Any bug can cause disease in any part of the body. It is a soil within which many a curriculum vitae has grown.

Still, you tend to play the odds and do not fret overmuch about rare infections in day-to-day medical care. Common things being common and all that.

I have mentioned in the past how much it annoys me that most case reports of unusual infections so often conclude that now bug x has been described causing disease y, it has to be in everyone differential.

No. It is an interesting curiosity, but I need not consider your once in a medical career infection in my differential diagnosis. But you do.

The patient is a homeless IVDA, heroin mostly, who comes in with pain. She has pain in the right supraclavicular area and her left heel.

At the first ER, she was dismissed as drug-seeking and sent out. Here's a pearl. Heroin uses do not come in drug-seeking. They can get all the drugs they need on the street much more easily than from the ER. Medical addicts may come in drug-seeking, but not street addicts.

The pain continued, and she came to one of my hospitals. This time she got a CT that showed a phlegmon behind the clavicle and nothing in the heel.

They called me. I found nothing in the foot (no rubor, dolor, calor, or tumor), and the CT looked like inflammation. The supraclavicular process responded rapidly to vancomycin and then po TMP/sulfa.

The heel pain improved less, and podiatry found no explanation for the pain either, so she went out on TMP/sulfa, only to return a few days later because of the heel pain. This time there was an MRI that showed osteomyelitis in the heel.

No way. The calcaneus does not get infected in adults outside of trauma, and the patient denies any trauma to the heel. There are a smattering of cases in kids, but I could lose a hand and still count the cases reported in adults. Heck, I need exactly one finger to count the reported the cases. I choose the pinky. It looks so Dr. Evil.

Since the blood cultures were negative, we opted to look at the heel in the OR. Soft bone and all the cultures grew MRSA.

Now debrided, it will be a course of vancomycin if the psychosocial comorbidities allow.

So now that I have reported a case of hematogenous MRSA osteomyelitis of the calcaneus as a cause of heel pain, you too must, must I say, consider it in a differential diagnosis for the next heel pain that you see.

See? I can he just as stupid as the next author. Perhaps more so.

Rationalization

J Am Podiatr Med Assoc. 1993 Dec;83(12):681-4. Hematogenous osteomyelitis of the calcaneus.

http://www.ncbi.nlm.nih.gov/pubmed/8283394

Chapter Twenty-Five

A Case From One of the Country's Best

Nov 21, 2014

I sometimes wish I could tell my referring docs, hey you ordered the test, you decide what it means. But it doesn’t work that way. The most common are EBV serologies on people with no syndrome consistent with EBV, and I get to be the final arbitrator as to the significance of a diagnostic test.

It became easier to weigh in on these cases this week when I received an email from the AVVO letting me know that using a

completely objective mathematical model…after analyzing a multitude of factors and criteria, the AVVO rating system has given you one of the highest scores in the country.

Just so you know, I am one of the elite attorneys in the country, rated a superb 9.3. Ha. Eat your heart out. Unfortunately, two other doctors in my hospital had the same award, diluting the honor. Who would have thought one hospital could have three doctors who are top attorneys and had never attended law school? What are the odds? But when I thanked the AVVO for the honor, it turned out to be an error. Sigh. So I will not order the plaque or put it on my CV.

Unbeknownst to me, it is common for some orthopedic surgeons to send of cultures during routine prosthetic joint revisions.

The patient had a hip placed 15 years ago, and for the last five years, the hip would ‘catch’ and cause him some pain. This worsened over the last month, so he had a revision. No fevers, no constitutional symptoms, no medical problems, no infections elsewhere. Preop labs were fine.

Intra-op the hip looked fine, and the pathology showed no infection. But.

Two tissue samples are growing Proteus in the broth only. So the orthopedic surgeon called me to decide what to do with the cultures. There is not a lot of clinical data to guide me.

Results: Three (15%) of the 20 revision arthroplasty patients had a single positive culture. Infectious Disease consultants diagnosed all three of these positive cultures as contaminants. None of the patients had a true-positive intraoperative culture. The total cost billed by the hospital to obtain these cultures in all 20 patients was $87,514.8

Discussion: In our study, obtaining a set of three intraoperative cultures for those patients with a negative preoperative infection workup was not only cost prohibitive but did not diagnose a single subclinical infection. Studies to find other more reliable, accurate, and cost-effective alternatives to diagnose PJI are warranted.

and

The reported incidence of false-positive cultures in revision total joint arthroplasty has been extremely variable, ranging from 3% to 52% and averaging more than 20%

and broth cultures are not that reliable.

The broth-only positive cultures showed poor sensitivity and positive predictive value but good specificity and negative predictive value. The good specificity indicates that it can help to rule in the presence of PJI; however, the poor sensitivity makes broth-only culture an unreliable screening test.

So nothing to suggest an infection, but the cultures are with an organism I would not want to call a contaminant as much as I want to. It is hard to ignore two positive cultures with the same organism.

The nice thing about ID is most of the time, I basically tell patients what they have to do: you have x, and we need to do y. Do what I say or die. But not this time. So I talked over the options with the patient and the potential outcomes. We decided on safe better than sorry and to treat the Proteus. I was not happy, but I would not have been happy no matter what we decided.

And I suggested to orthopedics that next time do not send cultures if the joint doesn’t look infected. As a former top lawyer, that is the best advice I could give.

Rationalization

Is There a Role for Routine Intraoperative Cultures to Diagnose Subclinical Periprosthetic Joint Infection During Revision Total Hip And Knee Arthroplasty?

http://www.msis-na.org/annual-meetings/2013-annual-meeting/2013-program/115-routine-intraoperative-culture

The Fate of the Unexpected Positive Intraoperative Cultures After Revision Total Knee Arthroplasty

http://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1006&context=orthofp

Performance Characteristics of Broth-only Cultures After Revision Total Joint Arthroplasty.

http://link.springer.com/article/10.1007/s11999-014-3507-z

Chapter Twenty-Six

Last Ditch Effort

Nov 24, 2014

The patient has a history of kidney stones and recurrent urinary tract infections.

Somewhere along the line, C. glabrata got into his collecting system, and he gets recurrent signs and symptoms of pyelonephritis: fevers, flank pain, vomiting, pyuria, and cultures that only grow C. glabrata.

There have been numerous attempts to remove the stones, but they recur/are refractory to removal by all the methods of urology.

At first, he was treated with fluconazole as the organism was sensitive. Evolution being what it is after several months symptoms recurred, and repeat testing showed that the MIC to fluconazole was off the wall.

So he was sent to me. I thought it would be best to try amphotericin B, but he is one of those patients who reacts quickly and decisively to lipid ampho. Within three doses, his creatinine was 5.5 despite the usual attempts to ameliorate renal toxicity.

The organism was still susceptible to voriconazole, so that was next. It worked. For a while. All the pyelonephritis symptoms resolved, and after a long course of therapy, we stopped the voriconazole. Soon, symptoms were back as was the pyuria, the C. glabrata, and now it is voriconazole resistant. I hate evolution.

So now what? Micafungin? Almost no data with this drug in the urinary tract:

The present report describes three cases of C glabrata-associated urinary tract infections successfully treated with micafungin. To the authors' knowledge, this is the first report of successful treatment of C glabrata and azole-resistant C albicans-associated urinary tract infection with an echinocandin.

Are three a case series? I suppose so. It is the classic definition (see addendum). There was an abstract with more patients and a similar result, but given that candiduria is often self-limited, it is difficult to know what to make of these cases, especially given the low urine levels of micafungin.

Following a single intravenous dose of 14C-micafungin (25 mg) to healthy volunteers, 11.6% of the radioactivity was recovered in the urine and 71.0% in the faeces over 28 days

Although perhaps if I used radioactive drug...

But with no other options, I gave micafungin a try, and after a month, the urine is sterile, and the pyuria is gone. And he now has hives.

Here's hoping it worked as I do not have any other options.

And I never saw the patient again.

Rationalization

Can J Infect Dis Med Microbiol. 2007 Mar;18(2):149-50. Treatment of candiduria with micafungin: A case series.

http://www.ncbi.nlm.nih.gov/pubmed/18923769

Micafungin treatment and eradication of candiduria among hospitalized patients

https://idsa.confex.com/idsa/2011/webprogram/Paper32551.html

Clin Infect Dis. 2007 Mar 1;44(5):e46-9. Epub 2007 Jan 22. Caspofungin in the treatment of symptomatic candiduria.

http://www.ncbi.nlm.nih.gov/pubmed/17278048

Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis - review of the literature

http://www.eurjmedres.com/content/16/4/159

Research Phrases Translation / Meaning

https://www.smart-jokes.org/research-phrases-meaning.html

It has long been known ... I didn't look up the original reference.

A definite trend is evident ... These data are practically meaningless.

Of great theoretical and practical importance ... Interesting to me.

While it has not been possible to provide definite answers to these questions ... An unsuccessful experiment, but I still hope to get it published.

Three of the samples were chosen for detailed study ... The results of the others didn't make any sense.

Typical results are shown ... This is the prettiest graph.

These results will be shown in a subsequent report... I might get around to this sometime, if I'm pushed / funded.

The most reliable results are those obtained by Jones ... He was my graduate assistant.

It is believed that... I think.

It is generally believed that ... A couple of other people think so, too.

It is clear that much additional work will be required before a complete understanding of the phenomenon occurs ... I don't understand it.

Correct within an order of magnitude ... Wrong.

In my experience ... Once.

In case after case ... Twice.

In a series of cases ... Thrice.

According to statistical analysis... Rumor has it.

A statistically oriented projection of the significance of these findings. A wild guess.

Thanks are due to Joe Blotz for assistance with the experiment and to George Frink for valuable discussions ... Blotz did the work and Frink explained to me what it meant.

A careful analysis of obtainable data... Three pages of notes were obliterated when I knocked over a glass of wine.

It is hoped that this study will stimulate further investigation in this field ... I quit.

Chapter Twenty-Seven

Pre-Thanksgiving Irritation

Nov 26, 2014

I have been ill all week. Some sort of viral grunge that is not bad enough to warrant staying home but bad enough to make functioning unpleasant. Damn, but the steps have gotten steeper. Fortunately, work is slow, and with a bit of self-isolation, I kept away from most patients. It wasn’t Ebola level PPE (I keep calling it PPI at meetings) but more than enough to keep patients safe from me. Infectious is the first name in my specialty, after all.

So perhaps it was the illness lowering my annoyance threshold, or perhaps I am just getting old and grumpy (hey, punk, get off my lawn), and the threshold is falling naturally. But some things just irritate me, like a barking dog on a quiet weekend morning.

Case in point. The patient is a middle-aged female in the US from Pakistan visiting family. She has diabetes and is a life long smoker and is a comfortably middle-class government official.

Forty years ago, she was treated for TB with a year and half of unknown antibiotics and had been fine since. She had three days of cough and fever, saw an MD, and the CXR followed shortly by a CT, showed a 3 cm cavity with no air-fluid level and only a modest rim. Usual differential diagnosis, but TB is at the top of the list.

The patient looks fine and says she feels fine. Just a little nonproductive cough the last few days. Risks and ROS are negative for any other process.

She actually brought her CXR from October, and the report reads no pathology.

So she is admitted, and sputum sent for culture and AFB.

And she is put on meropenem and vancomycin. Why? Because anaerobes and MRSA and Pseudomonas and any number of organisms COULD be causing this and since it COULD be causing it, there needs to be antibiotics given to cover it. Never mind that the patient looks fine, has a CXR/CT that is not realistically compatible with those organisms, and given the size of the cavity had probably been there a lot longer than three days. I think they were treating the differential, not the patient.

But here is what really annoyed me. That CXR from just a month ago? That was normal? Did anyone pull it out and look at it? Nope. I did. It wasn’t normal. Right where the mondo cavity is now, there were two small cavities just starting out their life. I swear no one looks at films anymore, they trust the report.

NEVER TRUST THE REPORT. LOOK AT THE FILMS YOURSELF. ALWAYS.

Sorry, I shouted.

Before I could get into full rant mode, the AFB came back positive, and the PCR identified it as MTB. Now she is on RIPE as they call it these days. INH should always come first on the list, but evidently, no one wants to say IRPE. It sounds like a newborn belch.

There are other interesting questions with the case. Over and above my old fart whinging. Which I have been doing a lot more of late. Is this reactivation or acquisition of a new strain of TB? What is the optimal therapy given the prior exposure to TB meds 40 years ago? How much of the TB is due to smoking and diabetes?

I have no definitive answers to the above, although there has been a tonne of studies on TB and either smoking or diabetes. Both diseases adversely affect all aspects of TB and its treatment.

For now, await cultures and look at the damn films.

And have a Happy Thanksgiving, Salmonella, and Campylobacter free.

Rationalization

Eur Respir J. 2014 Oct 30. pii: erj01142-2014. Smoking adversely affects treatment response, outcome and relapse in tuberculosis.

http://www.ncbi.nlm.nih.gov/pubmed/25359352

Arch Med Sci. 2014 Oct 27;10(5):1019-27. doi: 10.5114/aoms.2014.46220. Epub 2014 Oct 23. Tuberculosis and diabetes mellitus - an underappreciated association.

http://www.ncbi.nlm.nih.gov/pubmed/25395955

Arch Intern Med. 2002 Sep 9;162(16):1873-9. Tuberculosis recurrences: reinfection plays a role in a population whose clinical/epidemiological characteristics do not favor reinfection

http://www.ncbi.nlm.nih.gov/pubmed/12196086

Chapter Twenty-Eight

How did THAT get THERE?

Dec 1, 2014

The patient is a young female who had S. aureus tricuspid valve endocarditis a year ago secondary to IV drug use. She did well from an ID perspective but not from an addiction perspective, and she continued to use until three weeks before admission.

While in rehab, she developed the same symptoms as before: fevers and chills and some moderate pleuritic chest pain and so to the ER.

CT had multiple septic pulmonary emboli, and there was a vegetation on the TV.

This time the blood cultures have a gram-negative diplococcus in all the bottles, and there is one bottle with a viridans Streptococcus as well.

The MALDI-TOF calls it an N. mucosa.

Two mouth bugs in the blood and certainly on the valve.

"Do you lick the needle?" I ask.

"No" is the reply, with a look of disgust I get from all non-needle lickers.

So I explain to the patient the reason I asked. Many IVDAs lick their needles before injection, and that is the way the mouth bugs get to the valve.

And I get an ah-ah moment from the patient.

"I do lick the injection site if there is blood after I shoot," she says.

I never heard that variation before. Doesn't surprise me. When I get minor bloody trauma on my hands working around the house, the wound goes into my mouth without thinking. Kind of icky, come to think of it.

There are about 21 cases of N. mucosa endocarditis in the Pubmeds. Evidently, it can be a rather destructive beast and cause lots of emboli, which we see on the CT.

There is a case after tongue piercing and a polymicrobial case in an IVDA.

As to licking, I find the following quote:

Practices such as needle or skin licking prior to ‘shooting up’ may lead to contamination with organisms from the oral flora.

There is a case of Eikinella bacteremia in IVDA from wound licking, but the rest are Pasteurella due to animals licking wounds. No surprise as well as I have seen several similar cases in my career. My favorite was the girl who put tuna on her nose so the cat would lick it off. It is one way to get Pasteurella meningitis. And double ick, since pets also lick their butts.

So as best I can tell, this may be the first case of endocarditis from a human licking their skin.

And you know the rule: you must, must I tell you, always consider licking in your history. Especially if a Tootsie Roll pop is admitted with fevers.

Rationalization

J Infect. 2014 Jun;68(6):601-4. doi: 10.1016/j.jinf.2014.02.007. Epub 2014 Feb 20. Endocarditis due to Neisseria mucosa: case report and review of 21 cases: a rare and severe cause of endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/24561019

Clin Microbiol Infect. 2001 May;7(5):275-6. Endocarditis due to Neisseria mucosa after tongue piercing.

http://www.ncbi.nlm.nih.gov/pubmed/11422256

Aust N Z J Med. 1988 Dec;18(7):874-6. A case of polymicrobial infective endocarditis involving Neisseria mucosa occurring in an intravenous drug abuser.

http://www.ncbi.nlm.nih.gov/pubmed/3250412

Z Kardiol. 2004 Aug;93(8):618-23. [Piercing and tattoos in patients with congenital heart disease -- is it a problem?].

http://www.ncbi.nlm.nih.gov/pubmed/15338148

Shooting up: the interface of microbial infections and drug abuse

http://jmm.sgmjournals.org/content/60/4/408.full

J Infect. 1994 Jan;28(1):102-3. Eikinella corrodens septicaemia among drug injectors: a possible association with 'licking wounds'.

http://www.ncbi.nlm.nih.gov/pubmed/?term=8163821

Chapter Twenty-Nine

Three Dog Night

Dec 10, 2014

Did you miss me? I just spent the last week in the NE, wandering around Boston and Newport. Great time, although I will note that downtown Boston has the highest percentage of old, thin, well-dressed patricians with most sour looks on their faces of any city I have ever visited. Dudes: you are rich and live in Boston. Revel in it.

Oh well. Back to Portlandia.

My problem since returning is the number one. I have the understanding that one is the loneliest number that you'll ever do. One has also been the most common MIC in my gram-positives since returning.

Gram-negative rods tend to become resistant to antibiotics in a binary way. They acquire a new chunk of DNA, and the next thing you know, resistance.

Gram-positives can be sneakier. The slow accumulation of mutations in the cell wall results in an MIC that gradually heads upwards.

The MRSAs this week all have an MIC to vancomycin of 1. While not quite the level, 1.5, where treatment failure may become more likely, I still don't like it. Vancomycin stinks on ice under the best of circumstances, and the last thing I need is an obese diabetic with osteomyelitis and an MRSA with a vancomycin MIC of 1.0.

The calculus of ID: Sum enough risks over the course of a disease, and the odds of failure increase.

I also have a cirrhotic with myelodysplastic syndrome on dialysis with Streptococcus salivarius endocarditis with an MIC of 1.0 to penicillin. The decimal is in the wrong place.

I so much prefer to see a MIC's of 0.01 in my gram-positives. But easily killed bacteria are becoming a thing of the past, something to bore house staff with when I talk about the good old days.

One? Bad enough. But I have also been informed that two can be as bad as one. And inevitable.

Rationalization

J Microbiol Immunol Infect. 2012 Jun;45(3):214-20. doi: 10.1016/j.jmii.2011.11.006. Epub 2012 May 7. Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia.

http://www.ncbi.nlm.nih.gov/pubmed/22571999

Clin Microbiol Infect. 2004 Oct;10(10):899-903. Reduced susceptibility to penicillin of viridans group streptococci in the oral cavity of patients with haematological disease.

http://www.ncbi.nlm.nih.gov/pubmed/15373884

Chapter Thirty

True Name

Dec 12, 2014

In many fantasy novels knowing the true name of something gives you power over it. Know the name of the wind, and you can control it. The same holds true in infectious diseases. Know the full, true, name of the bug, and you may know not only how best to kill it, but perhaps it’s life story.

The patient comes in septic after a week of fevers and teeth chattering rigors, requiring the full panoply of ICU care to survive. Her only medical problem is a lack of a spleen, removed after a rupture as a teenager during a sporting event. Well, they didn’t remove it at the sporting event, but you know what I mean.

Of course, the worry is S. pneumoniae sepsis given the asplenia and this would seem to be confirmed by the mottled blue hands and feet as well as the gram-positive cocci in all the blood cultures.

Nope. It is first called a strep, then a S. bovis, but now it is S. gallolyticus with an MIC to PCN of 0.125. After five days, the WBC remains at 42K, so they call me. No surprise, the patient is on vancomycin, and the exam and ROS show nothing but mottled hands and feet.

The leukemoid reaction is simple enough: no spleen and total body ischemia. There are no reported cases of overwhelming sepsis, asplenia, and S. bovis, so perhaps that is a true-true-true and unrelated.

Given the lack of a source for the bacteremia, it is probably endocarditis, so the patient is changed to antibiotics more befitting an intermediately susceptible strep.

But what is the source? Bowel cancer, right? Maybe. But what is in a name? A bovis by any other name would have the same source. Deny thy microbiologist, and refuse thy name? Juliet had it easy:

The diversity of strains of S. bovis biotype II was analyzed, and it was confirmed that they belong to different species, either S. equinus or S. infantarius. It was demonstrated that S. gallolyticus, S. bovis biotype II.2, S. macedonicus and S. waius form a single DNA cluster separated into three different subspecies. They are delineated by different biochemical traits, limited DNA–DNA relatedness and noticeable divergence in 16S rDNA sequences. According to the current definition of species, the names S. gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. pasteurianus subsp. nov. and S. gallolyticus subsp. macedonicus subsp. nov. are proposed for these three subspecies.

The name makes a difference. S. gallolyticus subsp. pasteurianus means biliary disease:

The vast majority of biliary tract infections due to S. bovis group are caused by S. infantarius and S. gallolyticus subsp. pasteurianus (S. bovis biotype II), and nearly half of the bacteraemia due to these two species has a biliary source (43% of the S. infantarius and 56% of S. gallolyticus subsp. pasteurianus).

and cancers of the upper gi tract as well as lower:

Bacteraemia due to S. gallolyticus subspecies gallolyticus was significantly associated with endocarditis while S. gallolyticus subspecies pasteurianus was more likely to be associated with malignancies of the digestive tract, including gastric, pancreatic, hepatobiliary and colorectal cancers.

and

Streptococcus gallolyticus subsp. gallolyticus is a surrogate for endocarditis and/or bowel disease, whereas Streptococcus gallolyticus subsp. pasteurianus is a surrogate for hepato-biliary disease.

So I call the lab and ask for the real name. The MALDI-TOFF calls it S. gallolyticus subsp. pasteurianus, a name that makes me giggle. Past your anus. You are young once, but you can be immature all your life. Who says microbiologists don’t have a sense of humor.

Work up is currently limited by various organ instabilities. The CT shows an asymmetric gallbladder with fluid and sludge and a smattering of lymphadenopathy. The TTE is not normal but no vegetation. So various endoscopies are in her future. We will see where the name leads us.

Rationalization

Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus complex and related species: description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov..

http://ijs.sgmjournals.org/content/53/3/631.full

Clin Microbiol Infect. 2014 May;20(5):405–9. doi: 10.1111/1469–0691.12333. Epub 2013 Aug 30. Streptococcus bovis group and biliary tract infections: an analysis of 51 cases.

http://www.ncbi.nlm.nih.gov/pubmed/24033711

J Infect. 2014 Aug;69(2):145–53. doi: 10.1016/j.jinf.2014.03.010. Epub 2014 Mar 15. Bacteraemia due to Streptococcus gallolyticus subspecies pasteurianus is associated with digestive tract malignancies and resistance to macrolides and clindamycin.

http://www.ncbi.nlm.nih.gov/pubmed/24637236

Enferm Infecc Microbiol Clin. 2012 Apr;30(4):175–9. doi: 10.1016/j.eimc.2011.09.015. Epub 2012 Feb 28. [Diseases associated with bloodstream infections caused by the new species included in the old Streptococcus bovis group].

http://www.ncbi.nlm.nih.gov/pubmed/22377494

Chapter Thirty-One

Toxic See Mint

Dec 16, 2014

The patient had a hip and knee prosthetic joint infection as a complication of MRSA bacteremia that I think the source was blackberry scratches. I suspect that blackberries have a subtle, but malignant, intelligence. No matter how careful you are, it is impossible to pick more than a few blackberries without trauma. I think the plant moves in and gets you, a human blackberry trap.

Anyway, the MRSA seeded the knee and hip, and after a long attempt to salvage the joints fails, both are removed. Besides insulin-dependent diabetes and a half a pack a day smoker, no other medical issues. That is a sufficiency.

She is sent out on daptomycin (vancomycin allergy), and ten days later is back with a creatinine of 6.5. It is nonoliguric renal failure, and the UA is bland.

There are no urine eosinophils, and most cases of renal failure I could find with daptomycin are due to rhabdomyolysis. CK was normal.

Smarter heads than I ordered a tobramycin level. It was 1.6. The level was probably a lot higher a week ago. As is often the case, the cement spacers in the knee and hip were mixed with vancomycin and tobramycin. And in this case, not one joint, but 2 (although the surgeon cut his usual dose by a third). The vancomycin level was undetectable.

I never paid much attention to the antibiotics in the cement. It is what surgeons do, and it is not like they are going to change. I looked for good data as to their use in the treatment of infections. I found, well, little.

As a local drug delivery system, antibiotic-impregnated PMMA (polymethylmethacrylate) bone cements have been widely used for prophylaxis or treatment of deep infections after total joint replacement. However, the effectiveness of antibiotic-loaded PMMA in preventing infections after arthroplasty is still controversial. Furthermore, the outcomes of established deep infections treated with this technique are not consistent.

I spent the third quarter of the Spurs/Blazer game looking for a double-blind, randomized, placebo-controlled trial on antibiotic-impregnated cement for infection. Nothing. Really. Nothing. My google-fu is seriously off.

However, complications pop up in one search:

Eight patients had detectable aminoglycoside serum concentrations (mean 0.42 μg/mL; range 0.3 to 2.0); 1 patient had an aminoglycoside serum concentration of 0.9 μg/mL on postoperative day 38. Patients who did not have a detectable aminoglycoside serum concentration on the first postoperative day did not have a detectable concentration in the following serum samples. Six patients had elevation of serum creatinine by greater than 0.3 mg/dL from baseline.

and

Ten observational studies (n=544 patients) with clinical outcomes showed an average incidence of AKI of 4.8%. The average reported persistence or recurrence rate of infection was 11% during a follow-up period that ranged from 13 to 108 months. The risk-benefit ratio presently favors treatment although there appears to be higher complication rates and incidence of AKI than previously reported.

This blog is never an exhaustive review of a topic, it is what I can find on a question in about an hour. Much to my surprise, the use of antibiotic-impregnated antibiotics as treatment has no proven efficacy demonstrated by quality studies and only cost and toxicity.

The best you can say is that it has some efficacy as a prophylactic. And there is one issue I have with all antibiotic prophylaxis studies: how good were the basics of infection control: hand hygiene, scrubbing the hub, etc., etc. I strongly suspect that most of the time, prophylactic antibiotics is more a solution for sloppy essential infection control.

Rationalization

Ann Pharmacother. 2008 May;42(5):719-21. doi: 10.1345/aph.1K579. Epub 2008 Apr 1. Daptomycin-induced acute renal and hepatic toxicity without rhabdomyolysis.

http://www.ncbi.nlm.nih.gov/pubmed/18381844

ISRN Orthop. 2011 Aug 7;2011:290851. doi: 10.5402/2011/290851. eCollection 2011. Antibiotic-loaded cement in orthopedic surgery: a review.

http://www.ncbi.nlm.nih.gov/pubmed/24977058

Int J Artif Organs. 2012 Oct;35(10):832-9. doi: 10.5301/ijao.5000163. The use of antimicrobial-impregnated PMMA to manage periprosthetic infections: controversial issues and the latest developments.

http://www.ncbi.nlm.nih.gov/pubmed/23138709

Ann Pharmacother. 2012 Jul-Aug;46(7-8):929-34. doi: 10.1345/aph.1R049. Epub 2012 Jul 3. Systemic exposure to aminoglycosides following knee and hip arthroplasty with aminoglycoside-loaded bone cement implants.

http://www.ncbi.nlm.nih.gov/pubmed/22764326

J Arthroplasty. 2013 Oct;28(9):1490-8.e1. doi: 10.1016/j.arth.2013.02.035. Epub 2013 Apr 8. Two-stage arthroplasty for prosthetic joint infection: a systematic review of acute kidney injury, systemic toxicity and infection control.

http://www.ncbi.nlm.nih.gov/pubmed/23578491

J Arthroplasty. 2013 Oct;28(9):1490-8.e1. doi: 10.1016/j.arth.2013.02.035. Epub 2013 Apr 8. Two-stage arthroplasty for prosthetic joint infection: a systematic review of acute kidney injury, systemic toxicity and infection control.

http://www.ncbi.nlm.nih.gov/pubmed/23578491

A Systematic Review and Meta-Analysis of Antibiotic-Impregnated Bone Cement Use in Primary Total Hip or Knee Arthroplasty

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0082745

Chapter Thirty-Two

Not the other white meat

Dec 17, 2014

I am getting more irritable as I age. Things that used to elicit a ‘meh’ now result in poorly contained irritation.

Christmas cards are an example. I hate getting Christmas cards from health care institutions and insurance companies. That is not where health care dollars should go. And my billing company would send me a card every year, which means I was paying to get a card sent to me. I know it is only pennies, but it is the principle.

Stethoscopes also annoy me. Almost every picture of a doctor in ads has some $2 stethoscope around their neck, one no real physician who wanted comfort and good acoustics would ever use. Like the last Skeptical Inquirer cover. No doctor would use that stethoscope. And I suspect those big black frames have no lenses in them; they are there just to make the model appear smarter. Annoys me no end.

The patient is admitted with group A Streptococcus bacteremia/sepsis from cellulitis. She is young and obese and no other immunosuppression except diabetes.

Over the weekend, she has a fever and a bronchoscopy and the sputum cultures grow C. tropicalis and scant Aspergillus. A chest CT obtained for hypoxia is unimpressive for infiltrates. But no culture can go untreated, so micafungin was started. And THAT irritated me as well.

There is no clinical reason to suspect a fungal infection by history, and physical, the CT is not that of a pneumonia and Candida pneumonia is as rare as hen's teeth. So I gave in to my inner hissy fit to make a point, ranting that it was a waste of $350 dollars to give an antifungal with this clinical picture. There is no way she has a fungal infection and never treat yeast in the sputum. The micafungin was stopped, and the patient improved somewhat, although she has been hard to wean from the vent.

Shoot your mouth off at length (which defines an ID doctor), and there will be ample opportunity to make an ass of yourself. Especially if you like to pontificate in absolutes. The residents sent off a 1-3 beta-D glucan, and it came back greater than 500. Now what? Besides eating crow, which I prefer baked over the classic deep-fried. Is it a false positive?

Cefepime, which she was on at the time, might do it:

Seven antimicrobial agents tested positive for BG at the RVC: colistin, ertapenem, cefazolin (in vials), trimethoprim-sulfamethoxazole, cefotaxime, cefepime, and ampicillin-sulbactam in decreasing order.

and beta-D glucan is unreliable in ICU patients:

Thus, serum glucan levels did not show a correlation with the presence of fungal infections and did not appear to be specific for fungal infections.

Bacteremia leads to false positives:

For patients with bacteremia, the rate of false-positive results was much higher with the BG test than with the GM test (37% versus 2%, respectively; P < 0.0001), with no significant difference between Gram-positive and Gram-negative bacteremia.

But at a level of >500? I hate a positive test when the clinical picture is at odds with the result. No way clinically this is a fungal infection, and I would not have ordered the beta-D glucan.

I hate a positive test when the clinical pattern all points to a false positive, but a whopping false positive is hard to ignore.

So am I going to eat crow? Probably. And that annoys me as well.

Rationalization

Antimicrob Agents Chemother. Oct 2006; 50(10): 34503453. doi: 10.1128/AAC.0065806 Reactivity of (1’3)-²-d-Glucan Assay with Commonly Used Intravenous Antimicrobials

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1610103/

Clin Diagn Lab Immunol. Sep 2003; 10(5): 882885. doi: 10.1128/CDLI.10.5.882885.2003 Serum Glucan Levels Are Not Specific for Presence of Fungal Infections in Intensive Care Unit Patients

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC193887/

J Clin Microbiol. 2014 Jul;52(7):232833. doi: 10.1128/JCM.0356713. Epub 2014 Apr 16. Use and limits of (13)-²-d-glucan assay (Fungitell), compared to galactomannan determination (Platelia Aspergillus), for diagnosis of invasive aspergillosis.

http://www.ncbi.nlm.nih.gov/pubmed/24740084

POLL RESULTS

• Age makes me more
• intolerant 14%
• irritable 14%
• forgetful 31%
• incontinent 10%
• frightened 10%
• Other Answers 21%
  • sleepless, due to all the intolerant, irritable, forgetful incontinent, frightened people that I keep encountering on a daily basis.
  • easily amused.
  • humble
  • Wrinkled
  • Knowledgeable

Chapter Thirty-Three

The Attic is Filling Up

Dec 19, 2014

“I consider that a man’s brain originally is like a little empty attic, and you have to stock it with such furniture as you choose. A fool takes in all the lumber of every sort that he comes across, so that the knowledge which might be useful to him gets crowded out, or at best is jumbled up with a lot of other things, so that he has a difficulty in laying his hands upon it. Now the skillful workman is very careful indeed as to what he takes into his brain-attic. He will have nothing but the tools which may help him in doing his work, but of these he has a large assortment, and all in the most perfect order. It is a mistake to think that little room has elastic walls and can distend to any extent. Depend upon it there comes a time when for every addition of knowledge you forget something that you knew before. It is of the highest importance, therefore, not to have useless facts elbowing out the useful ones.” ~ Arthur Conan Doyle, A Study in Scarlet

I have certainly lost THAT battle. It seems anymore that my attic only contains the lyrics of songs. Certainly, I can’t remember past cases in real time. The case coming up? I have seen similar cases in the past, and the only way I know it is that a Google search came up with my prior blog entries.

And I remain annoyed no end as I go through references I know I have read to update my Compendium that I can’t recall half of them. At least I get to relive the joy of learning something new. Again. I wonder for those of us whose job it is to consume, digest, and then regurgitate information if we have our careers lengthened thanks to the Googles and PubMed functioning as a peripheral brain.

The patient is an elderly female on steroids for a skin disease. Three weeks ago, she was hospitalized with MSSA sepsis and was recovering at home on IV cefazolin when she developed an acutely painful, red leg, fevers, and leukocytosis.

She was admitted to the hospital. Exam showed a leg with rubor, dolor, calor, tumor, chronic small ulcers (unchanged), and hemorrhagic bullae.

It looked like group A Streptococcus except for the hemorrhagic bullae, which should lead to a consideration of V. vulnificans. I was thinking more embolic from endocarditis (despite a negative prior ECHO) than a specific pathogen. The patient was started on cefepime and vancomycin. The wounds and blood all grew?

Serratia marcescens. The heck.

I discovered I have written about this organism causing cellulitis and hemorrhagic bullae before. News to me.

Good thing I Google and Pubmed everything that comes my way. Shame I can’t reliably commit it to memory. Is my attic full? I don’t think so.

Although there must be a physical limit to how many memories we can store, it is extremely large. We don’t have to worry about running out of space in our lifetime.

The human brain consists of about one billion neurons. Each neuron forms about 1,000 connections to other neurons, amounting to more than a trillion connections. If each neuron could only help store a single memory, running out of space would be a problem. You might have only a few gigabytes of storage space, similar to the space in an iPod or a USB flash drive. Yet neurons combine so that each one helps with many memories at a time, exponentially increasing the brain’s memory storage capacity to something closer to around 2.5 petabytes (or a million gigabytes). For comparison, if your brain worked like a digital video recorder in a television, 2.5 petabytes would be enough to hold three million hours of TV shows. You would have to leave the TV running continuously for more than 300 years to use up all that storage.

So there should be plenty of room for more song lyrics.

She is slowing improving on cefepime, and the source of the Serratia is unknown; I assume community-acquired since we have no other cases in the hospital, and it is found in water.

Rationalization

Cockaroaches

http://boards.medscape.com/forums/?128@@.2a336d6e!comment=1

In Case After Case

http://boards.medscape.com/forums/?128@@.2a5716e4!comment=1

How Sweet It Is

http://boards.medscape.com/forums/?128@@.2a5b16b8!comment=1

Bloody Bullae

http://boards.medscape.com/forums/?128@@.29f59f76!comment=1,

this one last with song lyrics of which I am particularly proud. Oddly, I remember those.

POLL RESULTS

I think of my brain as

• an attic 5%
• a computer 20%
• a riddle, wrapped in a mystery, inside an enigma. 34%
• more spirochetes than neurons 19%
• jello 17%
• Other Answers 5%
  • A clay tablet in the rain
  • a valid reason to doubt that evolution works.

Chapter Thirty-Four

Failure

Dec 22, 2014

The patient was admitted with MSSA bacteremia of uncertain source. That’s endocarditis, although the TTE was negative, the patient defervesced right away and repeat BC were negative. Back pain led to an MRI that showed a paraspinous abscess.

In a perfect world, there would have been an I&D, but the surgeon was hesitant due to the patients body habitus, poorly controlled diabetes, and underlying cardiopulmonary problems.

So we elected to treat after percutaneous drainage of the abscess and opted for maximal dose cefazolin as the nursing home said nafcillin was too expensive. I was taught last century that cefazolin was not as good an anti-staphylococcal penicillin, but clinically that is probably not true:

The treatment failure rates were not significantly different at 4 or 12 weeks (10% [4/41] versus 10% [4/41] at 4 weeks [P > 0.99] and 15% [6/41] versus 15% [6/41] at 12 weeks [P > 0.99]). Cefazolin treatment was interrupted less frequently than nafcillin treatment due to drug adverse events (0% versus 17%; P = 0.02). Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.

and cefazolin is always always always better than vancomycin, the archetype mediocre antibiotic.

Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.

But there is one fine point for the MSSA: the MIC to vancomycin was 1.0. Here is the odd thing. Increased MIC to vancomycin may make beta-lactams less effective for MSSA:

However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 μg/mL, compared with those with lower MIC isolates (26.8% vs. 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not.

and

The association between elevated vancomycin MIC and 30-day mortality in SAB remained significant (p 0.001) on multivariable logistic regression analysis even when accounting for clinical factors. In addition, the association persisted when restricting analysis to patients with MSSA bacteriemia treated with flucloxacillin.

And now he is back with fevers, bacteremia, and the paraspinal abscesses are larger. TEE is negative at least.

We are sliding into the post-antibiotic era in some curious ways. Inadequate source control is more likely as the reason for failure than antibiotic choice, but he is now on nafcillin and heading to the OR.

Bad host, bad bug, bad source control. A perfect trifecta for failure.

Rationalization

Antimicrob Agents Chemother. 2011 Nov;55(11):5122–6. doi: 10.1128/AAC.00485–11. Epub 2011 Aug 8. Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia?

http://www.ncbi.nlm.nih.gov/pubmed/21825299

BMC Infect Dis. 2011 Oct 19;11:279. doi: 10.1186/1471–2334–11–279.

Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia.

http://www.ncbi.nlm.nih.gov/pubmed/22011388

J Infect Dis. 2011 Aug 1;204(3):340–7. doi: 10.1093/infdis/jir270. Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations.

http://www.ncbi.nlm.nih.gov/pubmed/21742831

Clin Microbiol Infect. 2013 Dec;19(12):1163–8. doi: 10.1111/1469–0691.12168. Epub 2013 Feb 26. Vancomycin minimum inhibitory concentration, host comorbidities and mortality in Staphylococcus aureus bacteraemia.

http://www.ncbi.nlm.nih.gov/pubmed/23441652

Chapter Thirty-Five

Trying to Put It Together

Dec 29, 2014

Work always slows down from Christmas to New Years. It is kind of odd. I used to think it was due to health care workers being on vacation and so the dip in infections was due to the lack of nosocomia. But we have driven hospital-acquired infections in my system into the dirt, and it is the usual infections that are not showing up. It appears that bacteria like to take a break over the holidays.

That should change soon. It is looking like it is going to be a bad flu season with a new H3 strain wandering the US. I figure when school starts up in a week, influenza will really take off:

The closure of schools has been postulated as a means of reducing transmission between children and hence reducing the number of cases at the peak of an epidemic; this is supported by the marked reduction in cases during school holidays observed across the world during the 2009 pandemic.

and combined with people going back to work

we show that commuting volume is highly correlated with the spread of ILI.

So while influenza is bad in some parts of the US now, it is likely to get a lot worse in January.

The one bug that doesn’t seem to take time off for the holidays is S. aureus. It is the one organism that has kept me occupied over the holidays.

The consult is a patient with MSSA bacteremia and a broken rib. Try to put those together. I tend to ask open-ended questions with patients, let them tell their story with as little prompting as possible, at least at the beginning. So much of the time, it is the direct, leading questions that get to the heart of the matter.

So the patient is admitted with four days of chest pain and fevers. That, in a nutshell, is the story as he tells it. The CT shows anterior chest wall inflammation/bleeding adjacent to a broken rib.

No trauma, he tells me—no hits or punches or falls or car accidents to account for the broken rib. I am not satisfied.

So any coughing illness?

Yep. He just finished a month-long cough, 'till he puked illness that sounds a lot like pertussis. But no chest pain from that.

So were you doing anything at the time pain started? Any kind of work or exercise?

Well, he lost weight with the coughing illness, so he started a work out program. As he was doing a pushup, he felt a tear in his chest, but he thought nothing of it until four days later when it became acutely worse.

So I am halfway there. The broken rib may be from the pushup, perhaps primed by the coughing illness.

We report a case of a patient with multiple rib fractures caused by cough. The diagnosis was performed by scintigraphy but fractures were not found in the X-rays. Five months later, a scintigraphy showed disappearance of the increased uptake areas. Multiple rib fractures are a cough complication which should be considered when the patient’s pain is persistent even if there is no X-ray evidence.

But where did the Staph come from? He denied any recent infection or cutaneous trauma with direct questioning.

But what are those? I asked, pointing to multiple areas of excoriation on his arms.

Bedbug bites. It has been a problem at my new house.

Now while any break in the skin can lead to an invasion by S. aureus, I am particularly enamored of the bedbug bite as

Bedbugs carrying MRSA and/or VRE may have the potential to act as vectors for transmission. Further studies are needed to characterize the association between S. aureus and bedbugs. Bedbug carriage of MRSA, and the portal of entry provided through feeding, suggests a plausible potential mechanism for passive transmission of bacteria during a blood meal. Because of the insect’s ability to compromise the skin integrity of its host, and the propensity for S. aureus to invade damaged skin, bedbugs may serve to amplify MRSA infections in impoverished urban communities.

So that is my story: cough weakens rib, pushup breaks it, there is bleeding, and it is seeded by S. aureus from a bedbug bite.

Maybe.

There is nothing to aspirate yet, and an infected rib fracture will be a real problem to treat. Rib osteomyelitis is also rare in humans with more reports in goats, whales, and foals. For now, it is cefazolin with plans to re-image for something to drain/biopsy in a week or so.

As you can see, I have a lot of time to think this week.

Rationalization

PLoS One. 2014 Jan 9;9(1):e83002. doi: 10.1371/journal.pone.0083002. eCollection 2014. Commuter mobility and the spread of infectious diseases: application to influenza in France.

http://www.ncbi.nlm.nih.gov/pubmed/24416152

Proc Biol Sci. 2011 Sep 22;278(1719):2753–60. doi: 10.1098/rspb.2010.2688. Epub 2011 Feb 2. Modelling the impact of local reactive school closures on critical care provision during an influenza pandemic.

http://www.ncbi.nlm.nih.gov/pubmed/21288945

Medicina (B Aires). 2008;68(5):380–2. [Multiple rib fractures associated with cough].

http://www.ncbi.nlm.nih.gov/pubmed/18977708

Bedbugs as Vectors for Drug-Resistant Bacteria

http://wwwnc.cdc.gov/eid/article/17/6/10–1978\_article

Environ Microbiol. 2014 May;16(5):1222–4. doi: 10.1111/1462–2920.12384. Epub 2014 Mar 3. Colonization of Cimex lectularius with methicillin-resistant Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/24589308

Chapter Thirty-Six

New Year, Same Issues

Jan 2, 2015

A new year. A time for resolutions, new beginnings, and fresh starts. An arbitrary opportunity to reinvent your life. I am ready for the New Year. Bring on 2016; I am tired of 2015.

What I really need this year is a way to kill MRSA, and the start of the year does not look optimistic for killing this beast.

The patient is admitted with MRSA consolidative/necrotizing pneumonia with bacteremia and neutropenia. And he has COPD and alcoholic cirrhosis. He has a lot of comorbidities, a virulent organism, and a bug that is hard to kill.

I have said it many times before that while there is no such thing as a strong, big gun or powerful antibiotic, there are antibiotics that, metaphorically speaking, stink on ice. Vancomycin is the archetype, static with poor pharmacokinetics and reasonably toxic. And as the MIC to vancomycin relentlessly creeps up, the ice is warmer, and the stink increases. Or more academically:

Taken together, the strain-to-strain variability in susceptibility to its bactericidal activity, the link between rising MICs and the development of heterogeneous intermediate susceptibility to clinical failures of therapy, and pharmacokinetic and pharmacodynamic issues that can impair effective delivery of drug to the site of infection have led to the consideration of alternatives to vancomycin monotherapy in the treatment of invasive MRSA disease.

What to do? Give the vancomycin, the tin standard, despite an MIC of 1.0 and a necrotizing infection we cannot remove?

I am leery about linezolid because of the bacteremia, and daptomycin is not to be used with pneumonia.

What else? Ceftaroline? I always prefer a beta-lactam if I can give a beta-lactam. I also detest extrapolating from the current inadequate lab and clinical data when deciding on treatment. Damned if you do, damned if you do.

I am also enamored of inhibiting the production of bacterial toxins/virulence factors in severe infections, but the data for MRSA is pretty thin gruel upon which to feed.

And there are so many antibiotic combinations that have been tried for treating S. aureus infections, none proved in a randomized trial. We have been trying to kill S. aureus for 50 years or so, and we still do not really know what is the best therapy for some of the worst forms of some disease and probably never will. It is too bad humans are not rabbits:

Ceftaroline, clindamycin, and linezolid considerably reduced mortality rates compared with the control, whereas vancomycin did not. Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.

Part of being a consultant is becoming comfortable with uncertainty and trying to synthesize insufficient information to come up with the best therapy. So I opted for ceftaroline and clindamycin. It was the choice that was the least unsatisfactory.

So far, not a good year for killing MRSA. I don’t see it getting any better any time soon.

Rationalization

Infez Med. 2011 Mar;19(1):42–4. Linezolid and clindamycin improve the outcome of severe, necrotizing pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).

http://www.ncbi.nlm.nih.gov/pubmed/21471746

J Antimicrob Chemother. 2010 Jan;65(1):24–36. doi: 10.1093/jac/dkp377. Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?

http://www.ncbi.nlm.nih.gov/pubmed/19861337

J Chemother. 2015 Feb;27(1):29–34. doi: 10.1179/1973947813Y.0000000156. Epub 2013 Dec 19. Methicillin-resistant Staphylococcus aureus nosocomial pneumonia patients treated with ceftaroline: retrospective case series of 10 patients.

http://www.ncbi.nlm.nih.gov/pubmed/24621164

Antimicrob Agents Chemother. 2014;58(4):1855–61. doi: 10.1128/AAC.01707–13. Epub 2014 Jan 6. In vivo efficacy of ceftaroline fosamil in a methicillin-resistant panton-valentine leukocidin-producing Staphylococcus aureus rabbit pneumonia model.

http://www.ncbi.nlm.nih.gov/pubmed/24395236

POLL RESULTS

I

• miss 2014 already 6%
• find 2015 a disappointment 12%
• can't believe in 6 years medical students will have been born in 2000 53%
• think it is 2166, and we are in the Matrix 15%
• each year is better than the one before. 15%

Chapter Thirty-Seven

Candidemia: Still not really knowing what to do.

Jan 6, 2015

I have an affinity for Candida. I spent three years of my life as an ID fellow working on how Candida adhered to endothelial cells. You would be hard-pressed to find a worse bench researcher, but I did develop an understanding of the virulence of this yeast. Candida are underappreciated for their potential to cause metastatic complications. But then, there is the same problem with S. aureus.

The patient is an elderly diabetic who has a protracted ICU course after a CABG. She has a fever, and 1 of 2 blood cultures grow C. albicans. They want to call it a contaminant, but I don’t think so. There is no such thing as a yeast being a contaminant in the blood, and a beta d glucan comes back later (still a send out in my system) elevated.

So it is real. But how long to treat? We work her up for complications and a source, and nothing. No fungus balls in the eye, the catheter tip negative, the repeat BC negative.

When I was an intern, when the only medication for Candida was amphotericin B, we would not treat a Candida in the blood beyond pulling the IV catheter in normal hosts. One of the many approaches to infections I have had to unlearn.

The Guidelines Say

If there are no metastatic complications, the duration of antifungal therapy is 14 days after resolution of signs and symptoms attributable to infection and clearance of Candida species from the bloodstream. This recommendation is based on the results of several prospective, randomized trials in which this rule has been successfully applied, and it is generally associated with few complications and relapses.

What we still do not know, at least to the degree we do with S. aureus, is what is the chance of a metastatic complication from a transient Candidemia and what level of 'few complications and relapses' is acceptable. We kind of know for the eye

Ocular involvement occurred in 16% of patients with candidemia; however, endophthalmitis was uncommon (1.6%).

Which makes the recommendation from the guidelines to get an eye exam on all patients a bit of an overkill. But my sense of guidelines is that they always suggest every test on every patient every time. Clinical judgment need no apply.

We do not know the risk of seeding other sites like disc, kidney, or liver. If you have had the misfortune of killing and dissecting large numbers of fungemic rabbits, as have I, you are aware Candida loves to cause metastatic infections. You also know that a lot of these metastatic infections are self-limited. So how many fungemias get treated that would go away on their own? We will never know.

So 14 days is reasonable in normal hosts, with no obvious complications who respond rapidly to therapy. Like I ever see those kinds of patients.

Rationalization

Clin Infect Dis. 2011 Aug 1;53(3):262–8. doi: 10.1093/cid/cir355. Ocular manifestations of candidemia.

http://www.ncbi.nlm.nih.gov/pubmed/21765074

POLL RESULTS

Guidelines

• are like the 10 commandments: always follow them 0%
• are like the 10 commandments: give them lip service 14%
• are like the 10 commandments: follow them when convenient, ignore them if they get in the way 53%
• are like the 10 commandments: nice in theory, rarely applicable in practice 28%
• are like the 10 commandments: are there for punishment if violated 3%

Chapter Thirty-Eight

Ignorance is Bliss. It is why I am so happy.

Jan 8, 2015

I write this blog because, like Jon Snow, I know nothing. Think about it.

Every one of these entries, two or three times a week, going back to September of 2008, is written to answer questions that I did not have an answer for. That’s about 650,000 words. With my SBM blogs, I have churned out well over a million words.

Amazing. And damn. How much I know is so dwarfed by what I want and need to know.

Today was a quick question outside the stairwell.

“How do you treat Archaea?”

“Huh? You mean the third domain of life, after Bacteria and Eukaryota?”

“Yep.”

“You don’t. They don’t cause disease in humans. They are extremophiles. Why would you want to do that?”

“A naturopath has diagnosed bowel overgrowth and is treating a patient.”

Well, I had never heard of that, and if you judge an idea by the company it keeps…

“That’s stupid. I don’t buy it.”

And I walked on up the stairs.

But as I walked up the steps, I thought, is it? What do I really know about Archaea and human disease? Nothing. And purveyors of pseudo-medicines do love to wildly extrapolate from preliminary basic science or small clinical trials to develop grand diagnosis and treatment schemes for all diseases. So maybe there is a nugget of truth of which I am unaware.

So I went to Pubmed. Yep bliss.

For it turns out that Archaea are part of the human gi tract and are responsible for the production of methane in the gi tract.

Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales,Methanobrevibacter smithii and Methanosphaera stadtmanae.

I suppose the colon qualifies as an extreme environment. I would not want to live in one. Archaea are found in about 50% of adults.

Methanogenic archaea are strict anaerobes that occur in a large range of environments, such as freshwater and marine sediments, soils and the gut of numerous animal species, including humans. Their physiology and ecology is widely studied for their intrinsic capacity to produce methane which is both an energy source (biogas) in bioreactor and a greenhouse gas emitted from natural and anthropic environments, including livestock. As a recurrent component of the human digestive tract, impact of archaea and more particularly methanogens on human health have been questioned for many years.

There are some intriguing associations between the presence of Archaea and colorectal cancer, obesity, IBD, IBS, diverticulosis, constipation (perhaps the most robust data), periodontitis, remembering the mantra that association is not causation. The review has a nice pro/con table of the evidence.

On author notes

It is important to consider the above findings using an evidence-based medicine approach. A recent meta-analysis evaluated the existing literature comparing the presence of methane and constipation. Although not all studies have confirmed these results, most do to support a significant association.

As the review notes

Links with diseases/human health, if any, will therefore be established in the next years, considering the archaea as a diverse population, as it is for bacteria, with more discriminant methods than methane in breath for methanogens… Genomics has strongly helped in the determination of their putative roles in the GIT, and indicated their unique metabolic properties before experimental proofs. This shows the potent physiological importance of the still poorly known domain Archaea in the human gut, and the role of its members, beneficial or deleterious, remaining to be determined.

And the ND connection? Evidently, it is considered part of bacteria of SIBO, Small Intestine Bacterial Overgrowth, for which Portland has a specialty ND clinic. With the usual pseudo-medical ability of making a mountain range from a grain of sand, besides IBS, according to the ND site, SIBO is associated with

Acne Roseacea, Acromegaly, Age: Elderly, Alcohol Consumption (moderate intake), Anemia, Atrophic Gastritis, Autism, Celiac Disease, Chronic Fatigue Syndrome, CLL (Chronic Lymphocytic Leukemia), Cystic Fibrosis, Diabetes, Diverticulitis, Dyspepsia, Erosive Esophagitis, Fibromyalgia, Gallstones, Gastroparesis, GERD (Gastroesophageal Reflux Disease) , Hepatic Encephalopathy (Minimal), Hepatic Steatosis, H pylori Infection, Hyprochlorhydria, Hypothyroid/ Hashimoto’s Thyroiditis, IBD (Inflammatory Bowel Disease) -Crohn’s -Ulcerative Colitis, IBS (Irritable Bowel Syndrome), Interstitial Cystitis, Lactose Intolerance, Leaky Gut, Liver cirrhosis, Lyme, Medications: Proton Pump Inhibitors, Opiates, NSAIDS Myelomeningocele, Muscular Dystrophy (myotonic Type 1), NASH/NAFLD (non-alcoholic: steatohepatitis/fatty liver disease), Obesity, Pancreatitis, Parasites, Parkinson’s , Prostatitis (chronic), Radiation Enteropathy, Restless Leg Syndrome, Rheumatoid Arthritis, Scleroderma.

And more. Color me skeptical. Perhaps yet another one true cause of all disease. I got me a hammer, look, everything is a nail.

The interactions of the microbiome and health and disease are in its infancy, and I find it fascinating. And it is cool that as one branch of the tree of life, we carry around the other 3. Or is it 4?

And I am another 900 words more knowledgable.

Rationalization

World J Gastroenterol. 2014 Nov 21;20(43):16062–16078. Archaea and the human gut: New beginning of an old story.

http://www.ncbi.nlm.nih.gov/pubmed/25473158

Am J Gastroenterol Suppl (2012) 1:28–33; doi:10.1038/ajgsup.2012. Methanogens in Human Health and Disease

http://www.nature.com/ajgsup/journal/v1/n1/full/ajgsup20126a.html

Microbiota, Antibiotics, and Obesity Tine Jess, M.D. N Engl J Med 2014; 371:2526–2528 December 25, 2014DOI: 10.1056/NEJMcibr1409799

http://www.nejm.org/doi/full/10.1056/NEJMcibr1409799

Giant viruses open Pandora’s box Genome of largest viruses yet discovered hints at ‘fourth domain’ of life.

http://www.nature.com/news/giant-viruses-open-pandora-s-box–1.13410

Chapter Thirty-Nine

Skin

Jan 9, 2015

We all have our weak points. Dermatology is mine. I hate making rash decisions. Wah Wah Wah.

Still. What is that rash?

The patient comes in with extensive cellulitis of the leg. Common enough. There are a lot of blisters filled with clear liquid, but that doesn’t concern me. It is common with erysipelas, although there is not a lot on the PubMed. The bullae look a lot worse than they are and ooze a lot.

Bullous involvement complicates erysipelas in some 5% of cases, with flaccid intraepidermal sterile blisters.

and

The clinical characteristics were well dermarcated (50 percent), erythema (100 percent) and oedema (85 percent), and bullae and vesicles formation (80 percent). Most presented with no pain (40 percent) and minimal signs of systemic toxicity… The most common predisposing factor was disruption in the skin barrier (65 percent), followed by venous insufficiency (20 percent) and lymphoedema (25 percent).

Although why the blisters I can’t find. Toxin mediated?

Frozen-section and conventional skin biopsy specimens revealed subcorneal intraepidermal cleavage. These cytological and histological findings are those of staphylococcal scalded skin syndrome (SSSS) and differ from bullous erysipelas or toxic epidermal necrolysis (TEN). Therefore bacterial exotoxins are most likely responsible for the intraepidermal blistering

Maybe. This form of cellulitis maybe polymicrobial:

Staphylococcus aureus was isolated from 7 (50%), while S. warneri, Streptococcus pyogenes and Escherichia coli grew from the lesions of 3 other patients. Six out of 7 S. aureus strains were methicillin resistant (MRSA)…Our findings suggest that S. aureus is frequently involved in and probably contributes in synergy with beta-hemolytic streptococci to the complicated course of bullous erysipelas.

She receives vancomycin and ceftriaxone (not from me, mind you), and the rash spreads everywhere, except the palms, soles, eyes, and tongue, and the WBC jumps to 25K. And under the erythroderma are hundreds of small pustules.

It does not look like any rash I have seen before. Since a picture is worth 1000 words, Google “acute generalized exanthematous pustulosis.”

Acute generalized exanthematous pustulosis. Never heard of it. It is an unusual drug reaction, and we are betting on the vancomycin as the cause.

The main culprit drugs are pristinamycin, amoxicillin, quinolones, hydroxychloroquine, anti-infective sulphonamides, terbinafine, and diltiazem, with a short exposure, ranging from hours to 15 days.

Although there have been case reports with a wide variety of other medications.

Three causes of a rash in one patient: inflammation, toxin, and allergic. Hickam’s dictum it is.

Rationalization

Singapore Med J. 2008 Oct;49(10):809–13. Blistering erysipelas: not a rare entity.

http://www.ncbi.nlm.nih.gov/pubmed/18946616

CMAJ. 2006 Aug 1;175(3):244. A blistering disease: bullous erysipelas.

http://www.ncbi.nlm.nih.gov/pubmed/16880441

Hautarzt. 1996 Oct;47(10):783–9. [Gram-positive septic-toxic shock with bullae. Intraepidermal splitting as an indication of toxin effect].

http://www.ncbi.nlm.nih.gov/pubmed/9036130

Dermatology. 2006;212(1):31–5. Bullous erysipelas: clinical presentation, staphylococcal involvement and methicillin resistance.

http://www.ncbi.nlm.nih.gov/pubmed/16319471

Br J Dermatol. 2014 Nov 15. doi: 10.1111/bjd.13540. [Epub ahead of print] Acute generalized exanthematous pustulosis: a retrospective audit of practice between 1994 and 2011 in a single center.

http://www.ncbi.nlm.nih.gov/pubmed/25399843

POLL RESULTS

My weakness is

• ID 8%
• Dermatology 21%
• maple bars 10%
• kryptonite 21%
• bad puns 31%
• Other Answers 10%
  • chocolate
  • bacon
  • debating myself, and too-often ending up on the losing team.
  • homemade bread

Chapter Forty

Where did those come from?

Jan 15, 2015

The patient, otherwise healthy, has two months of gradually progressive shortness of breath. She is increasingly unable to take her garden debris a half-mile down the road to the community mulch pile: no fevers, no cough, no night sweats, no weight loss. The rest of the PMH and exposure history was initially negative.

Screening labs are normal, but the CXR shows patchy multilobar pneumonia.

I sure wish we could just get rid of the CXR and CT everyone. So much more information is gained on CT, and the CXR misses so much pathology. I remember when the first CTs came online when I was a resident, and the resolution has only improved. Comparatively, CXRs are bear skins and stone knives to the CTs mnemonic memory circuit. If you do not get the reference, I feel sorry for you. It is a shame that CTs have that whole increased cost and excess radiation issue.

But the patient did get a CT, and it showed multifocal round infiltrates, tiny nodules, and some patchy alveolar infiltrates. Since she wasn’t bringing up any sputum, it was bronchoscopy time.

And the cultures grew moderate Aspergillus fumigatus. For cost reasons, she was placed on itraconazole, and over the next month, the shortness of breath gradually improved. But.

The cultures also grew Mycobacterium gordonae.

So, where did those come from?

The Aspergillus? On CT, the distribution would suggest a large inhalation as the cause, and she is a mulcher.

It was a dry, dusty summer in the NW, and this would not be the first inhalational infection I would credit to mulch. I have seen Nocardia and Aspergillus infections I think were from turning the mulch pile, and the googles would agree:

An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure.

The M. gordonae? That took a little more questioning. It is a water bug, so I started asking about their water. She lives in the country on well water that only goes through a paper filter they change once a month—no other treatment.

I think it is likely from the showerhead, and she is aerosolizing the bug into the upper airway. For example,

NTM grown from aerosols included M. abscessus (3 homes), M. gordonae (2 homes), M. kansasii (1 home), M. fortuitum complex (4 homes), M. mucogenicum (1 home), and M. wolinskyi (1 home).

I told her not to bother to culture her water. It would cost money, it is not a pathogen given her lack of co-morbidities, and there would be nothing to do about it anyway. It is likely part of the ecosystem of her water. Tap water is clean, not sterile.

I bet the M. gordonae is not a pathogen (she is getting better on the itraconazole). To call an atypical mycobacteria a lung pathogen requires multiple positive specimens over time and a compatible clinical syndrome, which she does not have. Yet.

And while she is at it, I told her to take the itraconazole with coke. It has acid-dependent absorption, and all soda pops (I call it soda pop, much to my wife’s annoyance. She thinks it should be called either soda or pop) have a low pH. Taking itraconazole will boost drug levels. Coke adds life afterall.

Rationalization

BMC Infect Dis. 2014 Nov 26;14(1):600. Gardening can induce pulmonary failure: Aspergillus ARDS in an immunocompetent patient, a case report.

http://www.ncbi.nlm.nih.gov/pubmed/25425351

J Clin Microbiol. 2013 Sep;51(9):3006–11. doi: 10.1128/JCM.00899–13. Epub 2013 Jul 10. Isolation of nontuberculous mycobacteria (NTM) from household water and shower aerosols in patients with pulmonary disease caused by NTM.

http://www.ncbi.nlm.nih.gov/pubmed/23843489

J Clin Pharmacol. 1997 Jun;37(6):535-40. Effect of a cola beverage on the bioavailability of itraconazole in the presence of H2 blockers.

http://www.ncbi.nlm.nih.gov/pubmed/9208361

Man dies after inhaling fungal spores from garden compost

http://www.theguardian.com/science/2008/jun/13/medicalresearch

“David Waghorn, a doctor at Wycombe hospital in Buckinghamshire and a microbiologist, said the man had been unlucky: “He’d been opening bags of compost and mulch which had been left to rot. The fungus spores had grown in perfect conditions. He was extremely unlucky - there must have been a very large number of spores which he inhaled.”

POLL RESULTS

I call it

• soda pop 4%
• pop 19%
• soda 40%
• coke (I'm in the South) 19%
• beer 5%
• Other Answers 13%
  • Either soda or pop, since I'm bilingual
  • soft drinks
  • soft drink (as opposed to sweet tea, the default beverage in the Deep South)
  • whatever is printed on the can or bottle, boring as that sounds. They all have brand names, you know.
  • soft drink?

Chapter Forty-One

Can't Tie It All Together

Jan 20, 2015

I’m missing something. And I don't mean I am a few cards short of a full deck.

The patient is a youngish male with a long history of kidney stones who is admitted with an exacerbation of the same.

As an outpatient, he had fevers, and cultures were done. The urine grew MRSA and Enterococcus.

The blood? Both sets grew Rothia mucilaginosa, which you probably know as Stomatacoccus.

After admission, more blood cultures are drawn. S. mitis, four bottles. Urine: negative.

Exam: nothing but flank pain. No cardiac findings and, importantly, no teeth. Full upper and lower dentures.

So neither organisms have been associated with renal stones, and there are only a smattering of cases of S. mitis UTI.

The usual rule is no teeth, no infections from viridans streptococci:

Streptococcus mutans and Streptococcus mitis predominates in the dentulous group, Streptococcus sanguis in complete denture group, Streptococcus salivarius in edentulous group and Streptococcus milleri in removable partial denture group.

Although as is the case, almost any bug can cause any infection, and there are the rare cases of infections like endocarditis in the edentulous.

So the blood cultures should not be coming from the urinary tract, they should not be coming from the mouth. The ECHO is negative for endocarditis (rock normal) and is the exam. I would think injection drug use would be on the list, but his current living situation makes that very difficult.

Munchausen's? It is suggested by the microbiology:

The unusual identity of these organisms from a thigh abscess led to the recognition that the illness was induced by self-injection with saliva,

But I hate that diagnosis and am loathe to jump to it too soon, although I am suspicious.

Thank goodness for time, as it will likely clarify the reason for the positive blood cultures. For now? I feel obligated to treat for endocarditis.

Rationalization

J Lab Physicians. 2013 Jul;5(2):144–5. doi: 10.4103/0974–2727.119876. Streptococcus mitis: An Unusual Causative Agent for Urinary Tract Infection.

http://www.ncbi.nlm.nih.gov/pubmed/24701115

Oral Microbiol Immunol. 1991 Apr;6(2):119–22. Are certain oral pathogens part of normal oral flora in denture-wearing edentulous subjects?

http://www.ncbi.nlm.nih.gov/pubmed/1945487

J Contemp Dent Pract. 2013 Jul 1;14(4):601–4. Comparative analysis of colony counts of different species of oral streptococci in saliva of dentulous,edentulous and in those wearing partial and complete dentures.

http://www.ncbi.nlm.nih.gov/pubmed/24309335

South Med J. 1979 Feb;72(2):225–6. Telltale mouth flora: a clue to the diagnosis of factitious recurrent thigh abscesses.

http://www.ncbi.nlm.nih.gov/pubmed/424800

Chapter Forty-Two

Wonder Drug

Jan 21, 2015

The patient is admitted with aspirin overdose. Not a common reason for an ID consult, but it was fun to see a process I had not really taken care of since I was a resident back in the Dark Ages. He had all the classic findings: gap acidosis, hearing issues, respiratory overcompensation. It also reminded me that I am glad acid-base is now someone else s problem.

But why the aspirin overdose? It turns out he is homeless and has leg pain from severe lymphedema. He was taking aspirin because that is the only medication he could afford.

I was asked to see the patient because of bilateral cellulitis. No, no, no. There is no such thing as bilateral cellulitis. What he had was a purulent cellulitis with a small abscess on one leg and lymphedema on the other. The lymphedema resolved with elevation, the infection did not.

Afebrile and no leukocytosis, I presumed it to be MRSA (it was) on the basis of the abscess and the pus over the cellulitis. But it did not look that bad for an MRSA.

As I was writing my note, I remembered, why I do not know, a letter in the NEJM from years ago that aspirin prevented S. aureus bacteremia in dialysis patients. I wondered if the aspirin could be having any effects on the cellulitis. Pubmed to the rescue. Yep.

Aspirin has a variety of effects on S. aureus that may be clinically relevant:

...recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASA s prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.

and

...our clinical hypothesis that aspirin has a clinically useful anti-staphylococcal effect in the dialysis population.

and

Little is known about the effect of salicylic acid, the major metabolite of aspirin, on the interaction between S. aureus and vascular endothelial cells. We examined the adhesion of S. aureus strain 8325 4 cultured with or without salicylic acid to human umbilical vein endothelial cells (HUVECs), and the ability of the strain to invade these cells. Strain 8325 4 cells grown in salicylic acid were significantly less adherent to and invasive in HUVECs.

and

In the present study, salicylic acid, the major in vivo metabolite of aspirin, mitigated two important virulence phenotypes in both clinical and laboratory S. aureus strains: alpha-hemolysin secretion and fibronectin binding in vitro. In addition, salicylic acid reduced the expression of the alpha-hemolysin gene promoter, hla, and the fibronectin gene promoter, fnbA.

Not a lot of information, but curious. Clinically relevant in this patient? Maybe. Fun to think about? Absolutely. But I still gave him a course of doxycycline.

Rationalization

Infect Immun. 2010 Mar;78(3):1339 44. doi: 10.1128/IAI.00245 09. Epub 2009 Dec 14. Salicylic acid diminishes Staphylococcus aureus capsular polysaccharide type 5 expression

http://www.ncbi.nlm.nih.gov/pubmed/20008532

J Infect. 2009 May;58(5):332 8. doi: 10.1016/j.jinf.2009.03.006. Epub 2009 Mar 20. Reduced valve replacement surgery and complication rate in Staphylococcusaureus endocarditis patients receiving acetyl-salicylic acid.

http://www.ncbi.nlm.nih.gov/pubmed/19342103

Am J Kidney Dis. 2007 Mar;49(3):401 8. Aspirin treatment is associated with a significantly decreased risk of Staphylococcus aureus bacteremia in hemodialysis patients with tunneled catheters.

http://www.ncbi.nlm.nih.gov/pubmed/17336701

FEMS Immunol Med Microbiol. 2007 Feb;49(1):56 61. Epub 2006 Nov 9. Effect of salicylic acid on invasion of human vascular endothelial cells by Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/17094786

J Clin Invest. 2003 Jul;112(2):222 33. Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/12865410

POLL RESULTS

The wonder drug that works wonders is

• aspirin. 27%
• sildenafil. 5%
• beer. 19%
• chocolate. 34%
• LSD man. It lets me feel the windows pain. 6%
• Other Answers 8%
  • Laughter.
  • Ondansetron
  • ethanol
  • 'Tussin

Chapter Forty-Three

A question but no answer.

Jan 26, 2015

This blog is often about the little things that pique my curiosity. I see something of interest, ask a question, and, thanks to the interwebs, I almost always find an answer. There are no questions that need to go unanswered, given the ease with which information can be found. I do not miss the Index Medicus

However, today I asked a question, and I cannot find a good answer.

The patient has multiple co-morbidities, and the question is whether there is a pneumonia. The sputum has pathogens, but she is afebrile and no leukocytosis. But she has a chronic white out of the left lung and a tracheostomy.

She is admitted for altered mental status, SIRS-y, and hypercalcemia from malignancy.

I am asked to weigh in on the presence or absence of a bacterial process. I do no think she has a pneumonia, but if there is an infection that can be difficult to exclude, it is pneumonia. Can’t prove a negative, right?

I am an old dog and have trouble with new tricks, which, as I understand it, are for kids. Troponins? Forgetaboutit. I come from a time of LDH isoenzymes to diagnose acute MI’s. No acute coronary syndromes for me, thank you very much.

And I have yet to include procalcitonin into my thought processes. Others seem to use it with drunken abandon, but any test with a

sensitivity and specificity of 76% (95% CI 0.66 to 0.84) and 70% (95% CI 0.60 to 0.79), respectively

is of little benefit in most ID cases. But that may be the old geezer in me talking.

Still, there were compelling reasons to both continue and stop the antibiotics, so I thought, why not let the procalcitonin be the tie-breaker?

If normal, there is data to suggest a procalcitonin, along with, oh, I don’t know, actually being a doctor by examining the patient and looking at all the relevant studies, is useful in helping to decide if antibiotics can be stopped. Nothing like giving clinical uncertainty a number, even if that number is actually uncertain. At least it is a number, and who can argue with a number?

But after sending the procalcitonin, I wondered: would the hypercalcemia mess with the result?

Calcitonin is released in response to hypercalcemia, and the patient is getting calcitonin. So is the lab going to be reliable? Got me. The Pubmeds have nothing, and the Googles are equally unhelpful.

In a rat model of pulmonary edema

Hypercalcemia increased nitrate/nitrite, MG, proinflammatory cytokines and procalcitonin levels. Pretreatment with calcitonin or L-Nil prevented these changes

and one reference states

Regulation of thyroid and inflammatory PCT are fundamentally different. C-cells of thyroid gland react to elevated calcium levels as well as to a number of other stimuli, such as glucocorticoids, calcitonin gene-related peptide (CGRP), glucagon, gastrin, and α-adrenergic stimulation to increase calcitonin release. Somatostatin and vitamin D suppress calcitonin production. Neither hypercalcemia nor any other of the above listed stimuli leads to release of PCT during inflammation.

So will it be reliable? Got me.

It came back not elevated. We stopped antibiotics. She did fine. Probably would have without the procalcitonin level.

Rationalization

Ann Emerg Med. 2007 Jul;50(1):34–41. Epub 2006 Dec 11. Procalcitonin test in the diagnosis of bacteremia: a meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/17161501

Dan Med J. 2012 Mar;59(3):A4357. The role of procalcitonin in adult patients with community-acquired pneumonia–a systematic review.

http://www.ncbi.nlm.nih.gov/pubmed/22381083

J Biomed Sci. 2008 Mar;15(2):227–38. Epub 2007 Sep 29. The detrimental role of inducible nitric oxide synthase in the pulmonary edema caused by hypercalcemia in conscious rats and isolated lungs.

http://www.ncbi.nlm.nih.gov/pubmed/17906944

A novel marker procalcitonin may help stem the antibiotic overuse in emergency setting

http://www.ijabmr.org/article.asp?issn=2229–516X;year=2013;volume=3;issue=2;spage=77;epage=83;aulast=Kaurref13

Chapter Forty-Four

Staph goes anywhere it wants

Jan 29, 2015

As I have said before, if I were a superhero, S. aureus would be my arch-nemesis. Like in the comics, no matter how many times it appears to be defeated, it comes back, a little harder to kill than the time before.

The patient is admitted with S. aureus bacteremia without a focus, shortness of breath, and pleuritic chest pain. He has what looks to be peripheral emboli in the feet. Maybe. They do not look like the emboli I have seen before; more of a vasculitis to my eye. There are a smattering of cases of vasculitis being set off by S. aureus, but I am probably overthinking it.

The CT shows multiple cavitating septic emboli in the lungs. With no findings to suggest a Lemmiers, it is presumptive right-sided endocarditis.

ECHO shows no vegetations or shunt, but that does not concern me overmuch, vegetations often fall apart and move downstream.

And there is a small pericardial effusion in the apex with no tamponade. What to make of that? Probably nothing but it does give me pause:

We included 479 episodes of IE from 459 patients (70% men, mean age 51 years). Small-to-moderate PE was observed in 109 episodes (23%) and large-to-very large PE was observed in 9 episodes (2%). Patients with small-to-moderate PE had a greater prevalence of intravenous drug use (38% vs. 23%) and more frequent right-sided IE than patients without PE (33% vs. 17%). Patients with large-to-very large PE had a higher rate of systemic emboli (22% vs. 18%) and periannular abscess (22% vs. 6%) than patients without PE. Renal failure was associated with a higher risk of PE (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.3); age was associated with a lower risk of PE (OR 0.98, 95% CI 0.97 to 0.99). One-year mortality of patients with IE with large-to-very large PE was higher than that of patients with small-to-moderate and absence of PE (56%, 18%, and 24%, respectively, p = 0.033). Large-to-very large PE increases the 1-year mortality of IE (OR 3.0, 95% CI 1.2 to 7.9). In conclusion, renal failure and younger age are associated with a higher risk of PE. Large-to-very large PE was associated with an increase in 1-year mortality.

Hemodynamically stable, we watch and wait. The blood grows MRSA with an MIC of 1.0 to vancomycin, but he responds to antibiotics with a decrease in fevers, and repeat blood cultures are negative.

Five days later, he has an increase in both shortness of breath and pleuritic chest pain. I assume one of the cavities had ruptured into the pleural space. It had. Someone more on the ball than I repeated the ECHO. Tamponade and so off the OR. Both the plural and pericardial space grew MRSA.

I have seen a handful of purulent pericarditis in my career, mostly S. pneumoniae. It is evidently not uncommon in autopsy series of endocarditis, but that is a select patient population.

Acute purulent pericarditis was observed in 22% of cases, mainly in patients with aortic valve IE and myocardial abscesses.

And there are only 25 hits on the Pubmeds searching for “pericarditis+bacteremia+aureus”, so despite the predilection of S. aureus to cause metastatic infections, the pericardial space is lower on the list.

All the pus is now drained, which is still the best therapy. I have a colleague who imitates me as a demented old man, slapping my thigh and yelling, “Drain the pus.” He is not too far off.

Rationalization

Am J Cardiol. 2013 Nov 15;112(10):1646–51. doi: 10.1016/j.amjcard.2013.07.024. Epub 2013 Sep 19. Risk factors for pericardial effusion in native valve infective endocarditis and its influence on outcome.

http://www.ncbi.nlm.nih.gov/pubmed/24055065

Clin Exp Rheumatol. 2006 Nov-Dec;24(6):705–6. Microscopic polyangiitis following recurrent Staphylococcus aureus bacteremia and infectious endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/17207390

Medicine (Baltimore). 2012 May;91(3):152–64. doi: 10.1097/MD.0b013e31825631ea.

Infective endocarditis at autopsy: a review of pathologic manifestations and clinical correlates.

http://www.ncbi.nlm.nih.gov/pubmed/22543628

POLL RESULTS

As dementia sets in, the last phrase I will say over and over is

• drain the pus 41%
• touched you last 5%
• beer please 20%
• pull my finger 11%
• I coulda been a contender. I coulda been somebody, instead of a bum, which is what I am 14%
• Other Answers 11%
  • Oh god, I wish I'd spent more time at the office.
  • Either Do you want fries with that or thank you, come again
  • Are we there yet?
  • Time to let the dog out!
  • whatever you do, don't be a nurse!
  • "Broken hearts are for assholes." (Zappa)

Chapter Forty-Five

Word Salad

Jan 30, 2015

The patient is a young female with five days of progressively severe headache. She comes to the ER for evaluation, and the initial workup is negative, and she was about to be discharged when she had a transient episode of word salad.

This led to an MRI (normal) and an LP: 230 lymphocytes, normal glucose, and a protein of 200. Aseptic meningitis.

After admission, she had one more episode of word salad but no other neurologic complaints.

Exam: afebrile, an aortic murmur (never noted in the past, but she is healthy) and a dermatomal vesicular rash on her back.

Shingles with an aseptic meningitis. Not uncommon.

It is the word salad that annoys me. Neurologic symptoms do occur with shingles but are rare and not associated with speech problems. I found a grand total of 2, and both were slurred speech. Usually, it is cerebellar ataxia:

The incidence of neurologic complications associated with varicella is estimated to be 1–3 per 10,000 cases. The central nervous system (CNS) manifestations that occur most frequently with varicella are cerebellar ataxia and encephalitis. Other rare neurologic complications include transverse myelitis, aseptic meningitis, and Guillain-Barré syndrome. Few data exist to help define the role of antiviral therapy for neurologic complications of varicella.

It is not an encephalitis as it only lasted minutes. Vascular? It acts like a transient ischemic attack.

HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years.

She is younger than 40 and that AV murmur gives me pause as a source for clot. The ECHO is going to be done as an outpatient to see if it is bicuspid.

What to do about it? I can’t see a need to IV acyclovir at this point; she is now neurologically normal and cannot relate the word salad directly to the thoracic sister. Aspirin? I might take it for two months if it were me, and I had an acute infection, but I sure wish there were more clinical trials than one, which was looking at MI post pneumonia.

Always more questions than answers.

Rationalization

Am J Med Sci. 2014 Sep 9. Varicella-Zoster Virus Vasculopathy: The Growing Association Between Herpes Zoster and Strokes.

http://www.ncbi.nlm.nih.gov/pubmed/25211583

Neurology. 2014 Jan 21;82(3):206–12. doi: 10.1212/WNL.0000000000000038. Epub 2014 Jan 2. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. http://www.ncbi.nlm.nih.gov/pubmed/24384645

BMJ Case Rep. 2013 Jan 9;2013. pii: bcr2012007575. doi: 10.1136/bcr–2012–007575. Herpes zoster as a cause of viral meningitis in immunocompetent patients.

http://www.ncbi.nlm.nih.gov/pubmed/23307457

Varicella-Zoster Virus: Atypical Presentations and Unusual Complications. J Infect Dis. (2002) 186(Supplement 1): S91-S98.

http://jid.oxfordjournals.org/content/186/Supplement\_1/S91.full

Coron Artery Dis. 2013 May;24(3):231–7. doi: 10.1097/MCA.0b013e32835d7610. Does aspirin use prevent acute coronary syndrome in patients with pneumonia: multicenter prospective randomized trial.

http://www.ncbi.nlm.nih.gov/pubmed/23283029

Chapter Forty-Six

Curiosities

Feb 3, 2015

It is easy to learn something new as there is so much I do not know. Currently, I have no facinomas, although I might. So many of my great diagnoses are disconfirmed by testing. The saying is when you hear hoofbeats, think horse, not zebra. So often, even the horse is an auditory hallucination.

Still, even if I do not have a diagnosis, I have some curiosities from the last few weeks.

One. I saw a patient a while back with severe pneumonia. She was on a ventilator with diffuse infiltrates throughout the lung. On admit her LDH was 500, PJP range, but the bronchoscopy had no PJP.

When I think of high LDH with pneumonia my differential diagnosis starts and stops with PJP. Histoplasma can give a high LDH as well, but Oregon is not Histoplasma territory, and the patient has no travel or exposure history. Oregon is a great place to live, but dull as dirt for infectious diseases.

Ever hear of lactate dehydrogenase elevating virus? Me neither. In 1960 it was discovered in mice and

belongs to part of the arteriviridae family and the nidovirales order. Also included in the nidovirales order are the coronaviridae.

It is only found in mice:

LDV has a remarkably narrow cell-type specificity, meaning nothing homologous with LDV in mice has been found in another species.

Or has it? There are two coronaviruses that increase the LDH: SARS and MERS CoV. (and as of 2020, COVID-19). Cue the music from jaws. But it turned out to be neither.

While her PCR on the BAL was positive for coronavirus, is was one of the coronaviruses that causes a cold. I can’t find where the usual coronaviruses have been reported to cause an elevated LDH or severe pneumonia. I conferred with higher-ups in public health as well. The LDH in this case was likely due to critical AS, probably rheumatic heart disease.

Two: Saw a patient in clinic who had an ichthyosiform rash. Ichthyo: fish like.

What was it? It turns out Portland has a Kava bar, and he likes to partake of kava. A lot. And kava use results in this kind of rash.

The beverage is a nonfermented depressant with complex neuropharmacologic properties that causes a tranquil state of intoxication. Kava also affects the skin, causing a peculiar scaly eruption. The cutaneous effects were first reported by members of Captain James Cook’s Pacific expeditions, but they have never been described in dermatologic literature. Heavy kava drinkers acquire a reversible ichthyosiform eruption, kava dermopathy.

I can't find the pathophysiology of the rash, but it will fade rapidly by stopping the kava.

LDV and kava skin. I love wandering across these curiosities.

Rationalization

Ann Acad Med Singapore. 2006 May;35(5):326–31. SARS in Singapore–predictors of disease severity.

http://www.ncbi.nlm.nih.gov/pubmed/16829999

Lancet Infect Dis. 2013 Sep;13(9):752–61. doi: 10.1016/S1473–3099(13)70204–4. Epub 2013 Jul 26. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study.

http://www.ncbi.nlm.nih.gov/pubmed/23891402

J Am Acad Dermatol. 1994 Jul;31(1):89–97. Kava dermopathy.

http://www.ncbi.nlm.nih.gov/pubmed/8021378

Chapter Forty-Seven

Little Things Matter

Feb 6, 2015

I am often fascinated by the little things, the factoids, and curiosities that may or may not make a difference.

The patient is an elderly female with a complicated urinary tract, a neobladder, and obstructing kidney stones who has an MSSA perinephric abscess that erodes/spreads into the right lobe of the liver.

The perinephric abscess is percutaneously drained and, since it is MSSA, she is placed on cefazolin.

Which I might have done. I was always taught not to use cefazolin instead of nafcillin, but recent studies have suggested that cefazolin is cheaper and less toxic than an anti-staphylococcal penicillin with equal efficacy:

Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.

But how about for undrained pus? There I am not so certain, as a follow-up CT several days later showed the abscess in the liver is larger. So they called me.

S. aureus churns out lots of beta-lactamase, and the pus can be full of it. As I can be, just not with beta-lactamase.

S. aureus can make one of at least four beta-lactamases, some of which can hydrolyze cefazolin:

Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D)…Whereas Km values of the four beta-lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta-lactamases for nitrocefin, cefazolin, and cephapirin…More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists. This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme.

and it may make a difference for endocarditis:

Analysis of the infecting strain disclosed a high minimum inhibitory concentration of cefazolin when a large inoculum was used, as well as rapid and complete cefazolin degradation, which was associated with regrowth in a time-kill experiment. DNA sequencing of the beta-lactamase gene showed that it was identical to that of the S. aureus type A beta-lactamase, known to efficiently inactivate cefazolin

and perhaps other S. aureus infections where the source is not controlled.

19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

So we got the liver abscess drained, and I changed the antibiotics to nafcillin. Unfortunately, I have no way to type the beta-lactamase made by this S. aureus .

The take-home: drain the pus and maximize the dose of cefazolin. The little things, like which beta-lactamase is present, may matter.

Rationalization

Antimicrob Agents Chemother. 2011 Nov;55(11):5122–6. doi: 10.1128/AAC.00485–11. Epub 2011 Aug 8. Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia?

http://www.ncbi.nlm.nih.gov/pubmed/21825299

Antimicrob Agents Chemother. 1992 Feb;36(2):440–5. Characterization of four beta-lactamases produced by Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/1605608

Relapse of type A beta-lactamase-producing Staphylococcus aureus native valve endocarditis during cefazolin therapy: revisiting the issue.

http://www.ncbi.nlm.nih.gov/pubmed/?term=14557964

Antimicrob Agents Chemother. 2009 Aug;53(8):3437–41. doi: 10.1128/AAC.00317–09. Epub 2009 Jun 1. Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure.

http://www.ncbi.nlm.nih.gov/pubmed/19487449

Diagn Microbiol Infect Dis. 2006 Mar;54(3):189–92. Epub 2006 Feb 8. Lack of association of Staphylococcus aureus type A beta-lactamase with cefazolin combined with antimicrobial spacer placement prosthetic joint infection treatment failure.

http://www.ncbi.nlm.nih.gov/pubmed/16466894

Chapter Forty-Eight

Take That

Feb 10, 2015

It’s baaaaaaaack.

The patient is admitted with an altered mental status and is discovered to have MRSA in both sets of blood cultures as well as a lower extremity (leg for you non-medical readers) cellulitis.

She had been hospitalized twice before at Outside Hospital with the same issue: MRSA bacteremia, but no cellulitis. The first time was six months ago when she was treated with six weeks of vancomycin, the second was three months ago with a six week course of ceftaroline.

Diabetes with triopathy and smoking are her main medical problems.

So is this a relapse or reinfection?

She never had a vegetation on ECHO on all three admissions, and I cannot imagine endocarditis with MRSA being silent for two months at a time.

So, where is the pus?

I keep coming back to the ever-annoying metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Why annoying?

An intensive search for metastatic infectious foci was performed including ¹⁸F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%).

Got that? Only the minority of patients had symptoms pointing to the infection. Now I do not want to get a PET scan and TEE on every patient with prolonged fevers. Damn it Jim, I'm a Doctor. I want studies guided by clinical signs and symptoms.

So what to do? Pan CT scan (or as my resident called it, the Answer Donut)?

Over the years, I have seen many a diabetic with a collection of pus in the arch of their foot that, because of neuropathy, was asymptomatic. And she did have was a cellulitis, although no ulcer on the foot.

So I started with an MRI of the foot before the Answer Donut. Pay dirt. Several small abscesses and most of her metatarsals were destroyed with MRSA. Osteomyelitis and soft tissue abscess is a good reason for recurrent bacteremia.

So I got use my clinical acumen after all. Take that metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

Rationalization

Medicine (Baltimore). 2012 Mar;91(2):86–94. doi: 10.1097/MD.0b013e31824d7ed2. Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

http://www.ncbi.nlm.nih.gov/pubmed/22391470

Chapter Forty-Nine

You Figure It Out

Feb 11, 2015

I note that I am prone to getting grumpy about issues that, once upon a time, would not have bothered me. The irritability of early dementia? Or just the phenomena that as people age, they’re less desirable personality characteristics sharpen and become more prominent. Few people actually get better as they age; we are not wine, but we do whine.

I have had a spate of outpatient consults of late to interpret Epstein Barr serologies.

They all present with a lack of an EBV syndrome: mononucleosis, typhoidal, lymphoma, sore throat and no supporting labs (cytopenias, atypical lymphocytes or transaminitis).

They have negative IgM but very positive IgGs to VCA and EBNA1. Sometimes they have several tests over time that wander up and down in the degree to which the IgG is reactive. Always problematic given that EBV is latent in B cells and can reactivate from a variety of other infections.

What the patients often have is a mild fatigue. I do not doubt that there is a post-infectious fatigue state from a variety of organisms as diverse as Epstein-Barr virus, Coxiella burnetii, and Ross River virus. But I doubt these patients had an active infection as the cause of their symptoms.

EBV in most patients is a marker rather than a cause of the symptoms. And there is nothing to be done for it anyway, recent small trials notwithstanding. So why send off the test if 0) there is no compatible syndrome 1) it is not diagnostic 2) there is no therapy and, most importantly, 3) you don’t know what to do with the result.

When I get these consults, I want to say to the referring physician: You ordered it, you figure it out.

But I can't. No point in further alienating my referral base. But here is my interpretation of the EBV serologies for the above scenario: Sanguis opus esse prudenter advertens.

Rationalization

World J Virol. 2012 Feb 12; 1(1): 31 43.vPublished online 2012 Feb 12. doi:10.5501/wjv.v1.i1.31vPMCID: PMC3782265 Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782265/

Mediterr J Hematol Infect Dis. 2010 Aug 10;2(1):e2010022. doi: 10.4084/MJHID.2010.022. EBV Chronic Infections.

http://www.ncbi.nlm.nih.gov/pubmed/21415952

BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033110/b102-mjhid 2 1 4

J Med Virol. 2013 Dec;85(12):2101 9. doi: 10.1002/jmv.23713. Epub 2013 Aug 19. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/23959519

POLL RESULTS

As I age I become

• more tolerant. 15%
• more irritated. 33%
• sadder. 3%
• funnier. 11%
• increasingly withdrawn into existential angst. 29%
• Other Answers 9%
  • Less likely to submit statistically meaningful poll responses.
  • drunker
  • I forget
  • I decided I'd just refuse to age.

Chapter Fifty

Making Do

Feb 16, 2015

The patient is an IV heroin user, homeless, uninsured, who comes in with a cellulitis of the forearm with a cord in the antecubital fossa. She is off to the OR, and a septic vein is removed.

They call me for the usual question: how to treat and with what.

One of three blood cultures has MRSA, as does the clot.

No stigmata of endocarditis, no prolonged fevers, negative ECHO.

Normally the type and duration of treatment of S. aureus is more around the bacteremia than the infection in the clot. The thrombophlebitis is now in the pathology lab, so that part of the infection is a cure. Treatment of S. aureus bacteremia should be treated with at least 2, often 4, weeks of IV antibiotics.

But did I mention she is a recalcitrant IVDA and homeless? Not the best patient for home antibiotics.

Interestingly, there is a series of IVDA patients with septic thrombophlebitis in whom a shorter course of IV antibiotics was successful:

In our study, the intravenous antibiotic treatment duration was quite variable, ranging from <7 data-preserve-html-node="true" days to >28 days. No relapse occurred in cases treated intravenously for >7 days. In more than one-half of the episodes (20 episodes; 56%), the patient received intravenous therapy for 21 days. The present data suggests that a 2–3-week course of intravenous therapy followed by therapy with oral antibiotics was safe for suppurative thrombophlebitis. Adherence in IDUs is known to be limited. Therefore, it remains uncertain whether the oral medications were taken.

And this may be a good opportunity for oritavancin as well, although it has not been used for bacteremia, only cellulitis. It is non-inferior to vancomycin for cellulitis, which is damning with faint praise, given that while there are no strong, powerful or big gun antibiotics, there are antibiotics that stink on ice. Like vancomycin.

But oritavancin is dosed every five days so I could avoid a central line. And it works in animals:

Once-daily intravenous administration of oritavancin was effective in methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, penicillin-susceptible and cephalosporin-resistant pneumococcal meningitis in rabbits, staphylococcal and enterococcal central venous catheter infections in rats, and 24-hour postprophylaxis of inhaled anthrax in mice...

and humans are animals. Except John Merrick.

So weighing all the pros and cons, a couple of doses of oritavancin and then finish up with po.

Postscript

Curious how practice changes. Five years later with linezolid cheaper and data to support its use, I would now treat with po or dalvabancin if IV needed,

Rationalization

Less than 28 Days of Intravenous Antibiotic Treatment Is Sufficient for Suppurative Thrombophlebitis in Injection Drug Users.

http://cid.oxfordjournals.org/content/46/5/741.full

Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections.

http://www.nejm.org/doi/full/10.1056/NEJMoa1310422

In vivo activity of oritavancin in animal infection models and rationale for a new dosing regimen in humans.

http://www.ncbi.nlm.nih.gov/pubmed/22431852

Chapter Fifty-One

Taps

Feb 19, 2015

I often get consults to treat unusual organisms. Sometimes I think, as if I know what to do.

The patient is a 50ish female with three months of refractory sinusitis that is mostly chronic: runny nose, fatigue, and mild maxillary pain at best.

CT shows both the sinuses are filled to the brim. But with what? Cultures grow Mycobacterium lentiflavum. Twice. A month apart.

I never heard of that one before. What to make of it? There are a smattering of infections on the Pubmeds but no cases of sinusitis. But. There is this interesting suggestion that chronic rhiosinusitis is associated with atypical mycobacterium found in plumbing.

And M. lentiflavum is common in some drinking water systems.

A total of 47 isolates from 36 patients were reported; 4 patients had clinically significant disease. M. lentiflavum was cultured from 13 of 206 drinking water sites. These sites overlapped geographically with home addresses of the patients who had clinically significant disease.

So I start asking questions. It turns out that she rinses her nose and sinuses every day with tap water and uses tap water in her CPAP. And the problem started after moving into her current apartment.

So I wonder if this is less of an infection and more of a continued exposure, perhaps even a hypersensitivity reaction, like is seen with M. avium and hot tubs.

Lots of speculation. Little data. While I await sensitivities, I suggested she use distilled/sterile water instead of tap water for nasal rinses and the CPAP and see if she improves so we can avoid antibiotics. Perhaps all she needs is to avoid the daily inoculation of mycobacteria.

I really should get cultures her tap water, but our lab doesn’t like to do environmental cultures from outside of the hospital, and it would cost the patient money she doesn’t have.

Never did give her antibiotics, she improved with a change in the water. Make of that what you will.

Rationalization

Human Infections Due to Mycobacterium lentiflavum

http://jcm.asm.org/content/40/2/728.full

Nontuberculous Mycobacteria in Household Plumbing as Possible Cause of Chronic Rhinosinusitis

http://wwwnc.cdc.gov/eid/article/18/10/12–0164\_article

J Clin Microbiol. 2013 Sep;51(9):3006–11. doi: 10.1128/JCM.00899–13. Epub 2013 Jul 10. Isolation of nontuberculous mycobacteria (NTM) from household water and shower aerosols in patients with pulmonary disease caused by NTM.

http://www.ncbi.nlm.nih.gov/pubmed/23843489

Emerg Infect Dis. 2011 Mar;17(3):395–402. doi: 10.3201/eid1703.090948.Mycobacterium lentiflavum in drinking water supplies, Australia.

http://www.ncbi.nlm.nih.gov/pubmed/21392429

Mayo Clin Proc. 2002 Nov;77(11):1233–7. Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use.

http://www.ncbi.nlm.nih.gov/pubmed/12440560jer

Chapter Fifty-Two

Not the Dog

Feb 26, 2015

The patient is a young female with acute lymphocytic leukemia. She is getting chemotherapy and comes in with neutropenic fevers.

History and physical are otherwise non-focal and, after pan-culture, she is started on antibiotics.

She rapidly improves both her WBC and fevers, and after 36 hours, one set of blood cultures are growing MSSA, and the other set has a gram-negative rod.

Several days go by when the lab finally calls it Capnocytophagia, and I am consulted.

It must be from a dog, I say. I had one patient whose dog chewed off their Groshong while they slept. I assumed somehow a dog contaminated the line.

But I looked more carefully at the report. Capnocytophagia species. Species? There are other Capnocytophaga? Guess so.

I called the lab. MALDI-TOF calls it Capnocytophaga sputigena. That is one of several (C. gingivalis, C. granulosa, C. haemolytica, C. leadbetteri, C. ochracea and C. sputigena) that are part of the human mouth. None of which I knew existed.

I once counted about 1200 organisms I need to know as an ID doc. An underestimate. 1206 may be closer to the mark. Capnocytophagia causes a hodgepodge of infections:

Systemic infections have been reported in cancer patients, especially with severe chemotherapy. These Capnocytophaga species can also cause a wide variety of infections in immunocompetent, as immonocompromised hosts, including bacteremia, endocarditis, pericardial abscess or coronary heart disease, lung infections, mediastinal or iliopsoas abscesses, empyema, various bone infections, keratitis, endophthalmitis, peritonitis, facial cellulitis (50, 65), suppurative lymphadenitis or abscesses, meningitis or extracerebral intracranial abscess. Peri-partum infections or preterm birth have been described, leading to chorioamnionitis and sepsis in the newborn.

Most of the reports are in chemotherapy patients where beta-lactamase production is common. It looks like clindamycin and beta-lactamase combinations are the best bet. The return of the WBC is probably an even better treatment. I worried more about the MSSA.

The patient did fine once the neutropenia resolved and finished up a course of antibiotics for the MSSA.

Rationalization

Capnocytophaga species.

http://www.antimicrobe.org/b92.asp

Clin Infect Dis. 2001 Aug 15;33(4):E20–2. Epub 2001 Jul 20. Bacteremia caused by Capnocytophaga species in patients with neutropenia and cancer: results of a multicenter study.

http://www.ncbi.nlm.nih.gov/pubmed/11462207

Clin Infect Dis. 1999 May;28(5):1172–4. Bacteremia due to Capnocytophaga species in patients with neutropenia: high frequency of beta-lactamase-producing strains.

http://www.ncbi.nlm.nih.gov/pubmed/10452663

Chapter Fifty-Three

Like Birding. But Interesting.

Feb 27, 2015

I have mentioned in the past the ID is like birding: there is a life list of organisms and infections I have seen and some I hope to see. Unlike birding, there are some infection I hope never to see: rabies, Ebola, and measles, to name a few.

Sometimes it's an 'oh, look at the odd bug there' consult. An organism that is rarely seen in a particular organ space, the ID equivalent of a Japanese striped knifejaw in an Oregon crab pot. Fishing and birding, I just realized, are very different pastimes with different outcomes despite the word similarity. Catch and release a condor? I think not. They taste better than chicken.

The patient is on CAPD and comes in with cloudy fluid, fevers and abdominal pain.

CAPD peritonitis. I see a case every couple of years. Usually a gram-positive of one kind or another. But not this time.

Cultures grow Neisseria elongata. I think that is a Lion King song. Maybe not.

There are a half-dozen cases of various Neisseria causing CAPD peritonitis, but no N. elongata. So mine is the first and, as a result, I am obligated to mention that now you, yes you, now and forevermore, need to consider this organism as a cause of CAPD peritonitis. As you may know, I hate it when authors suggest that since they saw a once-in-a-career infection, now I have to worry about the same organism. Nope. You will never, ever, see a case like this.

Most of the reported disease is endocarditis; I evidently saw a case in 2009. Like I remember.

A bigger question is why. He had a case of S. viridans peritonitis a year ago. It turns out he has bad teeth and occasionally has dental abscesses spontaneously drain into his mouth. Lack of dental insurance can be a bad thing.

The teeth are the likely source as N. elongata is found in the bacterial flora of the human pharynx, respiratory secretions, and blood. Although I do not think there is a bacterial flora of the blood. At least I hope so. Probably a bad sentence.

He is improving nicely on a third-generation cephalosporin. Now if we can just find a dentist…

Chapter Fifty-Four

2 B

Mar 3, 2015

Celebrity deaths come in threes. Infections can come in pairs. Not really. Just the wonderful delusion so beloved by the brain, seeing a pattern where none exists.

The first consult of the day was an elderly male with the sudden onset of fevers and rigors. He went to bed and awoke with a red, hot, swollen, and painful knee.

It is cleaned out and ?

S. agalactiae. He had none of the usual reasons for S. agalactiae infections in the elderly: cancer or diabetes. His chest X-ray showed an infiltrate, but he had zero pulmonary symptoms. Since S. agalactiae rarely causes pneumonia and is usually severe, it begs the question as to what is going on in his lung.

Talking to him, I noted a Band-Aid on his thumb.

What happened? I asked.

It turns out he has this odd vascular tumor that has been bleeding for three months. His doc has been trying to burn it off with no success. It is an odd fungating, oozing, vascular lesion.

I wonder if this was the source for the bacteremia, not unlike an Osler-Weber-Rendu patient. Given how hands wander, I do not doubt it could have been placed inadvertently in a source of S. agalactiae (GI tract).

No sooner do I finish the dictation than a call from another hospital. I have a patient with S. agalactiae in the blood for no reason, can you see her?

Well, she did have a reason with the more typical risks: diabetes and myeloma. She had the sudden onset of severe back pain and fevers and was admitted with altered mental status.

The MRI of her back was not read as discitis, but I am not so sure. There was some edema in both the disc and the endplates, but it was subtle. And she was better in a few days, but after 40, yes forty, mg of dexamethasone as part of her weekly myeloma therapy.

I wonder if the thalidomide, dexamethasone, and bortezomib made the usual changes on the MRI less evident; I can’t find much on the Pubmeds to support the hypothesis. Still, all that is back pain is not myeloma:

Previous dexamethasone therapy, together with an episode of bacteriemia, appears to be a predisposing factor for vertebral infection.

I elected to treat for a spine infection.

When I took my boards after my internship, there were a bunch of questions about S. agalactiae. I probably missed them all, never having heard of the organism. When I got home, I found out it was also known as Group B Streptococcus. I knew all about Group B Streptococcus except that it was also called S. agalactiae. I am still bitter.

Rationalization

Br J Haematol. 2003 Mar;120(6):1047–50. Infection—an underappreciated cause of bone pain in multiple myeloma.

http://www.ncbi.nlm.nih.gov/pubmed/12648075

Infez Med. 2014 Mar;22(1):50–6. Extra-cerebral severe infections associated with haemorrhagic hereditary telangiectasia (Rendu-Osler-Weber Disease): five cases and a review of the literature.

http://www.ncbi.nlm.nih.gov/pubmed/24651092

Clin Infect Dis. 2009 Jul 1;49(1):85-92. doi: 10.1086/599369. Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990-2007.

http://www.ncbi.nlm.nih.gov/pubmed/19480572

Chapter Fifty-Five

Living Up To Its Name

Mar 5, 2015

The patient is a 50-year-old male, no past medical problems, who has a shoulder repair, a Latarjet coracoid transfer procedure.

He does well for five days when it starts to swell and drain.

No pain, no fevers, no chills, no leukocytosis. Just swelling that comes to a head.

Thanks to the joy that is a cell phone, everything can be documented, and he has a video of the pus squirting out of his axilla, about a cups worth in a constant stream.

He has an I&D, and there is lots of pus, but no organism on gram stain and cultures remain negative at three days.

I am puzzled by the lack of any signs of infection, he is completely uninflammatory despite the huge volumes of rapidly accumulating pus. I would have expected some signs of infection.

Then day 4 and all the cultures grow P. acnes. Hmm.

The organism is not a surprise:

The proportion of patients with shoulder infection who had infection due to P. acnes was significantly greater than the proportion of patients with lower limb infection who had infection due to P. acnes (9 of 16 patients vs. 1 of 233 patients; P<.001 data-preserve-html-node="true" ).

nor are the normal labs

Patients with P. acnes shoulder infection typically present with normal laboratory values (white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)) making diagnosis difficult.

But I suppose if any bug is going to cause minimal symptoms, it will be P. acnes. Others have had the same issue:

The patient developed axillary abscess, without fever or pain, which was incised. Propionibacterium acnes grew in cultures… it reoccurred, with abscess formation that gradually increased in size during several weeks and reached 5×8 cm in diameter (figure 1A). C-reactive protein was elevated (94 mg/L), but the patient did not have fever.

But still. That much pus that fast should cause some symptoms. Nope. Just a giant post-op zit.

He did well with a washout and a long course of antibiotics.

Rationalization

Propionibacterium acnes Postoperative Shoulder Arthritis: An Emerging Clinical Entity.

http://cid.oxfordjournals.org/content/46/12/1884.full

Curr Rev Musculoskelet Med. 2015 Jan 18. Management of Propionibacterium acnes infection after shoulder surgery.

http://www.ncbi.nlm.nih.gov/pubmed/25596729

Knee Surg Sports Traumatol Arthrosc. 2014 Sep 11. Acute infection with Propionibacterium acnes after a Latarjet coracoid transfer procedure: a case report.

http://www.ncbi.nlm.nih.gov/pubmed/25209204

BMJ Case Reports 2013; doi:10.1136/bcr–2013–201090. Chronic Propionibacterium acnes prosthesis joint infection manifesting as a large abscess with gas, without prosthesis loosening.

http://casereports.bmj.com/content/2013/bcr–2013–201090.long

Chapter Fifty-Six

Horsing Around

Mar 6, 2015

Common things, it is often noted, are common. When you see a patient, you may want to find a zebra or even a unicorn, but most of the time, you get horses, although in ID, they may be Przewalski’s horses, African wild asses, onagers, or kiangs. And Przewalski's horses are far rarer than zebras, perhaps that should be the motto: When you hear hoofbeats, think Equus ferus caballus not Przewalski's. A more accurate and lovely obscurity that appeals to me.

The patient comes in with severe low back pain, can’t abduct his right leg, fevers, and rigors. The evaluation shows early discitis and an iliopsoas abscess.

Well, says Dr. Pontification, it is going to be S. aureus, probably an MRSA making the Panton-Valentine leucocidin given his WBC of 1.9. Probably had some minor trauma a few days before from trying to get his lawnmower started for the beginning of the grass mowing season. Good way to get a twisting groin pull, although the literature shows more infections from the trauma of the blades than yanking the cord. I have an electric for just that reason.

Nope.

Citrobacter koseri.

The patient is a middle-aged man with six weeks of fevers and chills who presents with a stroke. The exam has a murmur, TNTC emboli in the kidneys, brain and spleen, and a vegetation on his valve. There is some sort Streptococcus in his blood.

Well, says Dr. Pontification, given the duration of his symptoms, it is likely to be a viridans Streptococcus from his poor dentition. Coming from S. America I would be surprised if this was due to underlying rheumatic heart disease.

Nope.

S. agalactiae. Group B streptococcus.

That’s three S. agalactiae's in the last two weeks.

As best I can tell, acute endocarditis is a common presentation of Group B streptococcus, and the reports and series suggest that emboli and CNS complications frequently occur as was the case.

If I were to make a list of the top 20 organisms to cause these diseases, I do not think I would list either Citrobacter for discitis or S. agalactiae for subacute endocarditis.

I guess that is why we do cultures. And why Dr. Pontification needs to shut his yap, although I will say that people never remember when you were wrong, only the times when you predicted the onager.

Dr. Pontification loves the sound of his voice too much to ever be quiet.

Rationalization

J Paediatr Child Health. 2009 Sep;45(9):525–8. doi: 10.1111/j.1440–1754.2009.01552.x. Epub 2009 Aug 21. Infections following lawn mower and farm machinery-related injuries in children.

http://www.ncbi.nlm.nih.gov/pubmed/19702605

Med J Malaysia. 2012 Jun;67(3):337–9. Citrobacter koseri bacteraemia complicated by paraspinal abscess and spondylodiscitis—a case report.

http://www.ncbi.nlm.nih.gov/pubmed/23082432

Clin Infect Dis. 2002 Jun 15;34(12):1576–84. Epub 2002 May 24. Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962–1998.

http://www.ncbi.nlm.nih.gov/pubmed/12032892

Chapter Fifty-Seven

Testy

Mar 10, 2015

Tests. Can’t live with them, can’t live without them.

Tests drive me nuts. And they make me look the fool. What a surprise. Examples from the call weekend.

The patient has the new diagnosis of HIV, and dense bilateral infiltrates. He has been declining for an uncertain period and looks wasted, but neither infected ill nor short of breath.

His LDH is 180.

So, I say with great assurance, it isn’t PJP. In HIV, the LDH is ALWAYS elevated, especially with those infiltrates. So whatever is going on in the lungs, it isn’t PJP.

The sputum was positive for PJP.

Twenty-five years and I have not seen a PJP with a rock normal LDH.

Serum LDH has a high sensitivity for PCP (100% in this series) but must be interpreted with caution given its lack of specificity.

When I look in the literature, it appears that about 5% of PJP in AIDS will have a normal LDH, mostly with mild disease. CD4 are still pending, but I expect it to be close to zero. Still, with that severe a CXR, I would have expected some increase in the LDH.

My new addition to my list of rules: the more confidence with which you declare a clinical example, the higher the chance it will come back to bite you with a counterexample. Dr. Pontification, wrong again.

So the patient is a high school student admitted with fevers and a stiff neck. The CXR was read as abnormal (barely) so in addition to the LP there is a community-acquired pneumonia work up.

The LP had meningitis with gram-negative diplococci that didn’t grow due to prior antibiotics. But the Legionella urinary antigen was also positive. What?

Wrong CXR, no risks, wrong season, and we do not have Legionella in the great Pacific NW. Well, not much. Is this a false positive? No reports of Neisseria causing a false positive, but I think so. But why?

Here is where my brain hurts, trying to understand the biochemistry of the cell walls of bacteria. Wish me luck.

The Legionella antigen assay measures the 9–0-acetyly legionaminic acid, a form of lipopolysaccharide.

Does Neisseria make a similar cell wall components? Probably, and Campylobacter does as well. I think.

Legionaminic and pseudaminic acids are essential for flagellar assembly in Campylobacter spp., Legionella pneumophila, and Helicobacter pylori.

OK. And I think some of the articles suggest that Neisseria make legionaminic acid:

The NeuB proteins originating from Neu-pathways containing NeuD are more related to legionaminic acid syntases in pathways leading to the related sugar legionaminic acid than they are to NeuB-variants originating from Neu-pathways lacking NeuD (found in Neisseria and Campylobacter). This fits also well with the fact that the legionaminic acid gene clusters in C. jejuni NCTC11168 and L. pneumophila Philadelphia 1 also contain NeuD homologs whose putative function is to N-acetylate sugar precursors really similar to GlcNAc

I say with all the confidence of someone who has no real idea what the above paragraph really means but I think that the Legionella test is cross-reacting with Neisseria. I can only hope that someone with more knowledge than me will either confirm or deny my muddled understanding.

So a false negative, a false positive and microbiologic biochemistry. No wonder I was testy after the call weekend.

Rationalization

Swiss Med Wkly. 2011 Apr 29;141:w13184. doi: 10.4414/smw.2011.13184. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/21528464

Chest. 1995 Aug;108(2):415–8. Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis, and bacterial pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/7634877

Biochemistry. 2014 Feb 4; 53(4): 624–638. The Renaissance of Bacillosamine and Its Derivatives: Pathway Characterization and Implications in Pathogenicity.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951908/

Characterization of the sialic acid synthase from Aliivibrio salmonicida suggests a novel pathway for bacterial synthesis of 7-O-acetylated sialic acids.

http://glycob.oxfordjournals.org/content/23/7/806.full

Chapter Fifty-Eight

More Diagnostic Aggravation

Mar 11, 2015

The patient is young and healthy. He has had two weeks of fevers, rigors, and a progressive sore throat. He is finally admitted to the hospital with a WBC of 21K with 30% bands.

The rest of admit labs and CXR are normal.

Since there is no obvious cause of the fever, they call me.

I find a very ill male who notes a sore throat, a severe headache. No exposures of note. When I examine him, he has large tonsils but no exudate, and when I palpate the abdomen, he grimaces and slaps my hand away.

I am not really certain what is going on. Lemmiers? He is the right age. How does that explain the rebound? An abdominal issue like appendicitis? How does that explain the sore throat?

So we CT the neck and abdomen, and the answer is in the middle. A densely consolidated lower lobe infiltrate.

Another CXR missing a common diagnosis. Bleh.

49 patients (11.4%) were diagnosed by CT (p<0.001). data-preserve-html-node="true" These patients were younger (p<0.001) data-preserve-html-node="true" and more often complained of chest pain (p<0.001). data-preserve-html-node="true"

CONCLUSIONS:

Patients with pneumonia may present with normal or nondiagnostic CXR, although false negatives may be less common than previously reported.

and

CXR demonstrated poor sensitivity and positive predictive value for detecting pulmonary opacities. Reliance on CXR to identify pneumonia may lead to significant rates of misdiagnosis.

and

Of the 1,057 patients diagnosed with pneumonia, both CXR and CT were performed in 97 cases. Of this group, there were 26 patients (27%), in whom the CXR was either negative or non-diagnostic, but the CT noted an infiltrate/consolidation consistent with pneumonia. In our retrospective review of ED patients, we find that in 27% of cases in which both a CXR and a CT scan were performed in the work-up of varied chief complaints, pneumonia was demonstrated on CT in the face of a negative or non-diagnostic CXR.

It is too bad we can’t CT everyone: too expensive and too much radiation. Perhaps a CT that did just a few cuts, a slice through each lobe.

The future is probably portable ultrasound.

Bedside chest ultrasound is a reliable tool for the diagnosis of pneumonia in the ED, probably being superior to CXR in this setting. It is likely that its wider use will allow a faster diagnosis, conducive to a more appropriate and timely therapy.

We had a Grand Rounds on the topic, and I became a believer. I want a handheld ultrasound so I can check out all the infected organs on rounds. Not as a replacement for the radiology department but as an adjunct to my exam and stethoscope. It would be so much fun.

Now the issue is what is causing pneumonia; workup for the typical atypicals is cooking.

Rationalization

R I Med J (2013). 2014 Aug 1;97(8):20–3. False-negative chest radiographs in emergency department diagnosis of pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/25083953

Am J Emerg Med. 2013 Feb;31(2):401–5. doi: 10.1016/j.ajem.2012.08.041. Epub 2012 Oct 18. High discordance of chest X-ray and computed tomography for detection of pulmonary opacities in ED patients: implications for diagnosing pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/23083885

J Emerg Med. 2009 Apr;36(3):266–70. doi: 10.1016/j.jemermed.2007.11.042. Epub 2008 Jun 20. Chest radiograph vs. computed tomography scan in the evaluation for pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/18571356

Emerg Med J. 2012 Jan;29(1):19–23. doi: 10.1136/emj.2010.101584. Epub 2010 Oct 28. Lung ultrasound is an accurate diagnostic tool for the diagnosis of pneumonia in the emergency department

http://www.ncbi.nlm.nih.gov/pubmed/21030550

POLL RESULTS

The most unreliable common test that misses significant pathology is

• the chest X-ray 26%
• the physical exam 14%
• the MMPI 6%
• ABIM re-certification 10%
• drivers exam 42%
• Other Answers 2%
  • Polygraph test

Chapter Fifty-Nine

Spoke too soon

Mar 13, 2015

I have taken to reading the obituaries this year. I am not entirely certain why; I am not looking for patients or colleagues. Perhaps it is because I am of an age where I might have an entry sooner rather than later.

As I read the entries, I am struck by all the fabulous people who have died: caring, funny, charming, smart, curious, human beings whose existence brightened the world. I wonder where all these perfect people are; I certainly have yet to meet the people described in the obits. People certainly are much better in death. As a result, I have asked my wife that if she publishes an obit after I have gone that she only emphasizes my many faults.

One fault is to speak too soon.

Remember Wednesday's post? The one where I bitched about the CT showing a pneumonia that was not seen on the CXR. That was based on a verbal report from the hospitalist. Elvis had left the auditorium, so I did not get to look at the CT until the next day.

A picture is worth far more than a thousand words. To my eye, the CT had what looked liked multiple fuzzy peripheral septic emboli with one big quasi-nodular consolidation in the right lower lobe.

The blood was growing an anaerobic gram-negative rod that the MALDI-TOFF called Fusobacterium necroforum.

So it was Lemierre’s after all. Why no clot on the CT? I did not think you could Lemierre’s with a negative CT and no clot. But you can, kind of. It is why I so love PubMed.

Fusobacterium necrophorum can cause endemic pharyngitis and the Lemierre syndrome. Four previous case reports and one epidemiologic study have documented that some F. necrophorum pharyngitis patients develop bacteremia without developing the complete Lemierre syndrome. We report two more patients who have bacteremic F. necrophorum pharyngitis. We summarize the clinical presentation of these six patients. All received early diagnosis and excellent response to antibiotics. We speculate that prompt antibiotic treatment may have prevented the more serious Lemierre syndrome. Adolescents and young adults who present with significant pharyngotonsillitis and bacteremic symptoms should have blood cultures and receive antibiotic regimens that treat F. necrophorum. Recognition of such patients might prevent Lemierre syndrome.

Although it is more likely given the CT that all the clot just broke off and went downstream.

It is also amazing what antibiotics can do. Two days ago, he looked awful. Now? Bright-eyed and bushy-tailed.

Besides seeing the best cases, ID docs get to cure the best cases. Best job ever.

Rationalization

Laryngoscope. 2009 Aug;119(8):1552–9. doi: 10.1002/lary.20542. Lemierre’s syndrome: A systematic review.

http://www.ncbi.nlm.nih.gov/pubmed/19554637

J Neuroradiol. 2002 Jun;29(2):132–5. Lemierre syndrome: usefulness of CT in detection of extensive occult thrombophlebitis.

http://www.ncbi.nlm.nih.gov/pubmed/12297736

Clin Microbiol Infect. 2014 Oct 13. pii: S1198–743X(14)00045–7. doi: 10.1016/j.cmi.2014.08.020. [Epub ahead of print] The aetiology of pharyngotonsillitis in adolescents and adults. Fusobacterium necrophorum is commonly found.

http://www.ncbi.nlm.nih.gov/pubmed/25658556

Anaerobe. 2010 Dec;16(6):626–8. doi: 10.1016/j.anaerobe.2010.08.005. Epub 2010 Sep 8. Fusobacterium necrophorum bacteremic tonsillitis: 2 Cases and a review of the literature.

http://www.ncbi.nlm.nih.gov/pubmed/20813196

POLL RESULTS

When I die, I want my obit to emphasize

• my sense of humor 11%
• my wealth 0%
• that I was not half as smart as I thought I was 24%
• that I told them I didn't feel well. 27%
• that given this life, I will likely be reincarnated as an armadillo in a leprosy lab 24%
• Other Answers 13%
  • that I wasn't a jerk
  • that I am indeed dead, and all the blasted fundraisers can take me off their bloody mailing lists.
  • She has kept the faith.
  • that my favorite charities are accepting donations in my name.

Chapter Sixty

No Way. I Don't Think So

Mar 16, 2015

Way back in time, six months ago, the patient is admitted to Outside Hospital with fevers and two sets of blood cultures drawn a few minutes apart grew MRSA. Repeat blood cultures were negative, as was the TTE.

As she is a heroin user, the decision was made to treat as if endocarditis. Not unreasonable. I would. Although.

For this blog, I went looking for the data. If you have an IVDA with S. aureus bacteremia, what are the odds it is endocarditis? I know the data is out there, but I can’t find a good number. It all gets back to the classic article by Nolan and Beaty, which I have read dozens of times, and, although it is from 1976, it is still behind a damn paywall, and I can’t get to it. It is like having Shakespeare behind a paywall. By this time, it should be open source, free to the world. I’m not paying 30 bucks for it, that’s for sure. Someone can dig up their old photocopy and put the number in the comments.

The closest I could find was

Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis.

and

Statistically significant associations were found with the following: native valve disease (odds ratio [OR] = 4.5; 95% confidence intervals [CI] = 2.0– 9.9; p = .002), the presence of a prosthetic valve (OR = 10.5; 95% CI = 2.5–43.7; p = 0.0012), persistent bacteremia (OR = 7.4; 95% CI = 3.3–16.6; p = .0001), intravenous drug use (OR = 3.2; 95% CI = 1.2–8.6; p = .02), an unidentifiable portal of entry (OR = 3.3; 95% CI = 1.3–6.6; p = .008), a history of prior endocarditis (OR = 10.0; 95% CI = 2.0–50.0; p = .005), community acquisition (OR = 2.9; 95% CI = 1.4– 4.9; p = .004), and nonwhite race (OR = 2.5; 95% CI = 1.2– 5.3; p = .014).

Although IVDA, no portal and community acquisition are all kind of the same risk. While the chance of endocarditis is high, it is not 100%.

For the next 6 months, she was in and out of Outside Hospital, getting various shortened regimens of IV and PO antibiotics in an attempt to treat a presumed MRSA endocarditis.

Now she is in my hospital, having left Outside Hospital AMA after a week of IV vancomycin to try and definitively treat the presumptive endocarditis. I am asked to come up with a regimen to treat endocarditis, taking into consideration the numerous biopsychosocial roadblocks to a successful treatment plan.

No fever. No leukocytosis. No repeat positive blood cultures. Two negative ECHO’s. No emboli. An unimpressive heart murmur.

And she has lived for six months with MRSA on her valve with all those half-asses therapies? No way. I don’t think so. This isn’t endocarditis. It was a transient bacteremia half a year ago. I vote no antibiotics.

To be safe, we are going to get a TEE. If there is a vegetation, well, I like my words with maple syrup and sliced bananas.

Rationalization

Am J Med. 1976 Apr;60(4):495–500. Staphylococcus aureus bacteremia. Current clinical patterns.

http://www.ncbi.nlm.nih.gov/pubmed/1274983

South Med J. 1983 Sep;76(9):1131–5. Staphylococcus aureus bacteremia: a prospective study.

http://www.ncbi.nlm.nih.gov/pubmed/6612391

Rev Infect Dis. 1986 May-Jun;8(3):374–96. Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study.

http://www.ncbi.nlm.nih.gov/pubmed/3755255

Clinical Management of Staphylococcus aureus Bacteremia A Review.

http://jama.jamanetwork.com/article.aspx?articleid=1910116

A Prospective Multicenter Study of Staphylococcus aureus Bacteremia Incidence of Endocarditis, Risk Factors for Mortality, and Clinical Impact of Methicillin Resistance. \http://antimicrobe.org/Chang%20Endo%20Medicine%202003.pdf

Chapter Sixty-One

Small Things I Thought Were True

Mar 20, 2015

Well, mostly true. There are very few things that are 100% in medicine. Everything has an exception, except this sentence. Take that, Norman.

The patient had a bad gallbladder. She was too ill for a cholecystectomy, so a tube was placed in the gallbladder.

She did well, was sent home, only to return with a biloma and fevers. The song by the Knack, Biloma.

The fluid was drained and grew MRSA, E.coli, and Enterococcus faecalis.

I usually say that S. aureus and mixed infections are mutually incompatible. When you find S. aureus, you do not find gram negatives and anaerobes and vice versa, a clinical observation that has no real data to support it. All confirmation bias, I suppose.

How best to treat this abscess?

The usual rule is that you can’t treat Enterococcus with cephalosporins. Except for ceftriaxone, which is synergistic with ampicillin against Enterococcus. The one exception. Or is it?

I wonder hows about ceftaroline? Maybe.

we show that ceftaroline exhibits killing activity against our laboratory-derived ampicillin-resistant E. faecium mutant that overproduces a wild-type PBP5 and that ceftaroline inactivates PBP5 much faster than benzylpenicillin and faster than ceftobiprole.

and

MICs for Enterococcus faecalis were from 0.25 to 8 mg/L;

and

Ceftaroline was additionally active against coagulase-negative staphylococci (MIC₉₀, 0.5–1 mg/L), Enterococcus faecalis (MIC₅₀, 2 mg/L)...

So kinda sorta. I wouldn’t treat endocarditis with ceftaroline alone, but a drained polymicrobial abscess with no bacteremia? It seems a good choice will awaiting the gallbladder to ‘cool off’ before removal, which is what I was always told is the way to go. Although

We recommend that laparoscopic cholecystectomy can be done safely and successfully within 72 hours of presentation. There is no benefit to attempting to “cool off” the gallbladder. The message remains the same for acute cholecystitis: “get it while it is hot.”

Sometimes I think everything I know is wrong.

Rationalization

Antimicrob Agents Chemother. 2013 Dec;57(12):6358–60. doi: 10.1128/AAC.00923–13. Epub 2013 Sep 23. Activity of ceftaroline against Enterococcus faecium PBP5.

http://www.ncbi.nlm.nih.gov/pubmed/24060866

J Antimicrob Chemother. 2007 Aug;60(2):300–11. Epub 2007 Jun 4. In vitro activity of ceftaroline (PPI–0903M, T–91825) against bacteria with defined resistance mechanisms and phenotypes.

http://www.ncbi.nlm.nih.gov/pubmed/17548456

J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv17–31. doi: 10.1093/jac/dkq252. Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: results from an international surveillance study.

http://www.ncbi.nlm.nih.gov/pubmed/21115451

Antimicrob Agents Chemother. 2014;58(3):1494–500. doi: 10.1128/AAC.02274–13. Epub 2013 Dec 23. Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium.

http://www.ncbi.nlm.nih.gov/pubmed/24366742

Laparoscopic Cholecystectomy In Acute Cholecystitis – Experience From A Single Centre.

https://ispub.com/IJS/27/2/10067

Norman from Liar's Paradox

https://www.youtube.com/watch?v=wlMegqgGORY

Chapter Sixty-Two

Going ape? Monkey business?

Mar 23, 2015

I don’t know. One of the things that annoys me with headlines is the obvious pun. You see it all the time in acupuncture articles, some variation of point or needle. It is like when you ask the patient how they feel, and they reply, “with my fingers.” Oh gee, thanks, I never heard THAT one before. On the other hand, I have had complaints that my titles are a wee bit obtuse and obscure the content.

I see a lot of positive TB tests, both PPD and quantiferons, and the reasons are usually mundane. Not this one

The patient is a zookeeper in Asia, and there is an outbreak of TB in his primates. While he is in an area of high TB endemicity, I suspect he was exposed to the TB doing the post-mortems on the monkeys. There are, by his report, less than perfect conditions to prevent the spread of TB. Interestingly, all the primates have miliary disease with little in the way of pulmonary symptoms.

An autopsy is a good way to acquire TB:

By contrast, among personnel present during the 3-hour autopsy, the test results of all five nonreactors converted from negative to positive (mean reaction, 24 mm). Two of these persons had a positive sputum culture 8 weeks later. The DNA fingerprints of all three isolates were identical.

CONCLUSIONS:

A patient who did not transmit tuberculosis before death released a prodigious number of tubercle bacilli during autopsy.

It is not often you see 'prodigious' in a conclusion.

It is no surprise that TB can infect our cousins, since

tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought

TB goes back and forth from non-human primates as well as other animals:

Mycobacterium tuberculosis was diagnosed in two Asian elephants (Elephas maximus), three Rocky Mountain goats (Oreamnos americanus), and one black rhinoceros (Diceros bicornis) in the Los Angeles Zoo.

and we had a small TB outbreak in the elephants at the Oregon Zoo. TB has been spread from humans to elephants and back in the US. About 50% of Indian elephants have latent TB, so if Horton has a cough (My favorite Dr. Seuss book), wear an N95.

INH at 20 mg/kg is 433 300 mg capsules for the average 6500 kg elephant. That’s a lot of pills, about a third of a pound. We can even give Mycobacteria to our dogs and acquire it from our cats.

TB may have beaten Columbus to the New World in a seal, and MTB complex DNA has been found in 17,000-year-old North American bison. It is not just MTB, other pathogenic AFB can jump back and forth from animals to humans. Badgers carry M. bovis, give to cows, and then to humans. And on and on. Human to animal and back again.

Mycobacteria are one honey badger—a honey badger with Mycobacterium bovis.

Rationalization

Ann Intern Med. 1995 Jun 15;122(12):922–5. The risk for transmission of Mycobacterium tuberculosis at the bedside and during autopsy.

http://www.ncbi.nlm.nih.gov/pubmed/?term=7755227

The zoonotic importance of Mycobacterium tuberculosis : transmission from human to monkey : case report.

http://reference.sabinet.co.za/sa\_epublication\_article/savet\_v69\_n2\_a7

The risk of tuberculosis transmission to free-ranging great apes.

MMWR Morb Mortal Wkly Rep. 1993 Jul 30;42(29):572–6. Tuberculosis in imported nonhuman primates—United States, June 1990-May 1993.

http://www.ncbi.nlm.nih.gov/pubmed/8332115

Tusko becomes third elephant at Oregon Zoo to contract tuberculosis.

PLoS One. 2012;7(11):e49548. doi: 10.1371/journal.pone.0049548. Epub 2012 Nov 16. Serodiagnosis of tuberculosis in Asian elephants (Elephas maximus) in Southern India: a latent class analysis.

http://www.ncbi.nlm.nih.gov/pubmed/23166708

The truth about bovines, badgers and the spread of TB.

http://www.theguardian.com/science/2012/nov/11/alice-roberts-bovine-tb-badgers

Ancient DNA Suggests Seals Brought Tuberculosis to New World.

http://www.history.com/news/ancient-dna-suggests-seals-brought-tuberculosis-to-new-world.

Mycobacterium tuberculosis Complex DNA from an Extinct Bison Dated 17,000 Years before the Present.

http://cid.oxfordjournals.org/content/33/3/305.short

Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0010005

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000160

Mycobacterium tuberculosis Transmission from Human to Canine.

http://wwwnc.cdc.gov/eid/article/10/12/04-0094\_article

First documented cat-to-human TB infection revealed.

http://www.theguardian.com/society/2014/mar/27/first-documented-cat-human-tb-infection

Setting the Thresholds of Potential Concern for Bovine Tuberculosis.

http://www.sanparks.org/docs/conservation/scientific/mission/TPC\_BTB.pdf

Chapter Sixty-Three

Splash

Mar 26, 2015

Blood and other body fluids can end up in the oddest places. Over the years, I have had some peculiar exposures. Well, I have been asked about exposures. Thirty years in ID and I have not had a professional BBF exposure. My personal life is none of your business.

In the first year of practice, a patient was admitted with fevers and a diffuse total body red rash. This was back in the dark ages before we took exposure to body fluids seriously. I remember, with a shudder, that my dentist never wore gloves. Ew.

About half the residents saw the patient and, as was the style of the day, touching the rash with bare hands. I don’t remember that hand hygiene was even a consideration.

It was secondary syphilis.

The skin of secondary lues is filled with spirochetes, I imagine waving like fields of spiral wheat.

The treponemal burden in the various lesions, with the exception of the macular lesions, constitutes additional proof that all lesions represent progressive stages of the same lesion.

But how infectious is the skin? All the references say very or extremely or highly, but I never have been able to find a number or a rate.

So a bunch of house staff got a benzathine penicillin shot. Never, ever, touch a rash if you do now know what it is.

Recently a HCW had a blood splash in the eye from a patient that turned out to have latent syphilis. How infectious is that? No clue.

There is an interesting literature of syphilis being spread with blood transfusions, the earliest from the BMJ in 1939, but not much of a risk today with testing.

As best I can tell, there has not been transmission of syphilis from a blood and body fluid exposure in the workplace, although there have been a few prophylactic treatments.

I think it would be impossible in the IVDA population to know if the spread of syphilis would be from needles or the old-fashioned away.

As best I can tell, the risk of an eye splash is minimal. But I advised a shot of penicillin. Who wants to get primary ocular syphilis? Which, I found out, was a problem at the turn of the century. Just where were they putting their eye?

Primary ocular lues is said to be very rare but just why this should be true has always been a mystery to me Inasmuch as it has been demonstrated by different authorities that patients with a primary luetic lesion may be reinfected by inoculation ie by transfer of excretion from the lesion to other portions of the body it seems strange that the eye is not the site of primary lues in a greater number of instances. The most common modes of infection are a the practice of infected adults kissing children on the eyes and by the now fortunately almost obsolete custom of attempting the removal of foreign bodies from the eye by licking the lids…That primary ocular syphilis is rare, considering the various possibilities of infection.

The things I learn about writing this blog. Double Ew. But cool.

Rationalization

Clin Microbiol Rev. 2005 Jan; 18(1): 205–216. Secondary Syphilitic Lesions.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC544174/

Sex Transm Dis. 2012 Aug;39(8):588–90. doi: 10.1097/OLQ.0b013e3182515764. Acquired secondary syphilis in preschool children by nonsexual close contact.

http://www.ncbi.nlm.nih.gov/pubmed/22801339

Genitourin Med. 1993 Apr;69(2):102–7. The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws.

http://www.ncbi.nlm.nih.gov/pubmed/8509088

Br Med J. 1939 Feb 11;1(4075):264–6. Transmission of Syphilis by Blood Transfusion.

http://www.ncbi.nlm.nih.gov/pubmed/20782109

J Microbiol Immunol Infect. 2006 Aug;39(4):321–7. Occupational blood and infectious body fluid exposures in a teaching hospital: a three-year review.

http://www.ncbi.nlm.nih.gov/pubmed/16926979

The American Journal of Syphilis, Volume 4 1920.

Chapter Sixty-Four

Fetid Dingoes’ Kidneys

Mar 27, 2015

For my Puscast, I review a little over 2000 journal titles, download about 200, read 100, and talk about 40 a month. I was once told never to bother with a paper that has an enzyme in the title, and that is a useful guideline when skimming the literature. Many of the articles are reviews of obscure diseases that I make a note of, but figure I will never see. The problem is, once you read an article, you WILL see the disease in the next 90 days.

The patient is an elderly male who, six months ago, had Listeria bacteremia treated at Outside Hospital. She did well and, besides her age, had no risks for Listeria:

Compared with persons <65 data-preserve-html-node="true" years with no underlying conditions, those with chronic lymphocytic leukemia had a >1000-fold increased risk of acquiring listeriosis, and those with liver cancer; myeoloproliferative disorder; multiple myeloma; acute leukemia; giant cell arteritis; dialysis; esophageal, stomach, pancreas, lung, and brain cancer; cirrhosis; organ transplantation; and pregnancy had a 100–1000-fold increased risk of listeriosis.

I see the patient now for a red, tender prosthetic knee. He tells me it has bothered him since it was placed three years ago, always swollen and tender.

So I figure a coagulase-negative Staphylococcus or P. acnes.

Nope. A tap of the knee grows Listeria. Did not see that coming.

A month or so ago I came across Listeria monocytogenes-associated joint and bone infections: a study of 43 consecutive cases and I thought, huh, I’ll never see this, and filed the article in memory, one I need to know exists but do not really need to read carefully in the era the Googles. Best way ever to subsequently see a case.

Is the joint infection the cause or result of the bacteremia? Do not know.

Chronic joint infections with Listeria are reported

Infection of the device with Listeria monocytogenes occurred and persisted for 2 years.

It looks like the knee will need to come out,

Antibiotics, primarily amoxicillin (80%) with aminoglycosides (48%), were prescribed for a median duration of 15 weeks (range, 2–88). Eighteen patients (50%) underwent prosthesis replacement; all were successful after median follow-up of 10 months (range, 1–75). Five of 13 patients for whom material was not removed had protracted infection despite prolonged antibiotherapy; 3 of these patients later underwent prosthesis replacement with sustained recovery.

Although given that this is his third prosthetic knee and his advanced age maybe not the best option. So perhaps debridement and chronic suppression?

While I know the Secret is a crock of fetid dingo’s kidneys, I really need to come across an article about a Portland ID doctor winning Powerball.

Rationalization

Clin Infect Dis. 2012 Mar 1;54(5):652–60. doi: 10.1093/cid/cir902. Epub 2011 Dec 9. Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis.

http://www.ncbi.nlm.nih.gov/pubmed/22157172

Clin Infect Dis. 2012 Jan 15;54(2):240–8. doi: 10.1093/cid/cir803. Epub 2011 Nov 18. Listeria monocytogenes-associated joint and bone infections: a study of 43 consecutive cases.

http://www.ncbi.nlm.nih.gov/pubmed/22100574

J Med Microbiol. 2009 Jan;58(Pt 1):138–41. doi: 10.1099/jmm.0.004234–0. Chronic prosthetic joint infection caused by Listeria monocytogenes.

http://www.ncbi.nlm.nih.gov/pubmed/19074666

Int J Clin Pract. 2004 Apr;58(4):420–1. Delayed presentation of prosthetic joint infection due to Listeria monocytogenes.

http://www.ncbi.nlm.nih.gov/pubmed/15161131

POLL RESULTS

So it will come true in the next three months, I need to read a journal

article about

• winning Powerball. 28%
• the demise of the ABIM MOC. 6%
• weight loss without diet and exercise. 34%
• shooting under par. 3%
• peace, love, and understanding 28%

Chapter Sixty-Five

What. Me Worry?

Mar 30, 2015

I read a recent article about the future of ID, and the author mentioned that on rounds, he stops more antibiotics than he starts.

Been there done that. One of my colleagues will consult me just so the antibiotics can be stopped. A hand-holding consult with a hospitalist who doesn’t need my help given her excellent clinical skills.

I sometimes think I am the only doctor in the hospital who can ignore cultures, and I know I am the only one who understands the significance of cultures. We recently reviewed the S. aureus bacteremias at one of my institutions, and I was a little amazed at the number of patients who did not get an ID consult (about a fifth) but was not amazed at the suboptimal results.

No one would treat cancer without an oncologist or deliver a baby without OB help, but I am still surprised at how often people treat serious infections when they have no clue WTH they are doing.

So I am asked what antibiotic to send the patient home on for their pneumonia. He is an elderly male with sleep apnea, a known aspirator, and a tracheostomy. He had pneumonia last month and is admitted with a fever. One spike at home. None since. No leukocytosis, no fevers, no SOB, no increase in sputum, CXR no dense infiltrate, and the CT with some bibasilar crud, like every patient has in the ICU. And if his wife had not taken his temperature, he would not have known he was ill.

But he has positive cultures: MRSA and Pseudomonas grow from his sputum, and he has been on therapy for several days. Cultures through a tracheostomy mean little:

Quantitative aerobic and anaerobic cultures were performed on 28 tracheal aspirates from 16 clinically stable patients with tracheostomies. There were an average of six isolates per specimen, and the mean bacterial concentration was 106.9 organisms per milliliter. The numerically dominant bacteria were aerobic and facultative gram-negative bacilli. Anaerobic bacteria were recovered from just nine specimens (32 percent); and, when present, these organisms were found in relatively low concentrations. Repeat cultures obtained 30 to 60 days later from the same patients showed substantial changes in flora, but the numerically dominant species tended to persist. Cultures of saliva and throat swabs collected at the time of tracheal aspiration showed that there was little correlation between the bacteriologic findings from the upper and lower airways.

although they are helpful when

Tracheal aspirate cultures correlate with PSB cultures in patients receiving long-term ventilation who have clinical pneumonia, and they can be used to direct initial antibiotic therapy in this group of patients.

Key phrase: who have clinical pneumonia. My patient had no clinical signs or symptoms of pneumonia.

I suppose there are several ways you could interpret this collection of facts depending on your inclination and clinical paranoia: Early pneumonia. Tracheobronchitis. Aspiration. Colonization.

I favor the last. I do not think the patient has an infection and certainly not one due to MRSA or Pseudomonas. He should be sicker than stink, not watching a movie on the iPad.

The only thing antibiotics will do for him is breed resistance, and increase cost and toxicity.

I can see where one might err on the side of treatment. There is a worry meter with any disease where there is uncertainty, and few diseases have as much clinical uncertainly as pneumonia. The longer I do this, the more meter gets closer to zero. I am the Alfred E Newman of ID.

He went out on no antibiotics and did just fine.

Rationalization

Quantitative tracheal bacteriologic and cytologic studies in patients with long-term tracheostomies.

http://journal.publications.chestnet.org/article.aspx?articleid=1683632

Chest. 1994 Aug;106(2):531–4. Tracheal aspirate correlates with protected specimen brush in long-term ventilated patients who have clinical pneumonia.

http://www.ncbi.nlm.nih.gov/pubmed/7774332

Chapter Sixty-Six

Central Gas

Apr 2, 2015

People usually freak when they see gas in tissues. They think it means gas gangrene, C. perfringens.

And it can. But it is more important how the patient is doing and what the clinical risks are rather than that there is gas.

As I have mentioned in the past, the endpoint of all metabolism is the production of gas, and as the father of two teenage boys, I can confirm that this gas can be produced in prodigious amounts.

Still, occasionally I see gas in a place that gives me pause.

The patient is a middle-aged male with a week of fevers and neck pain. Several years ago, he had a fusion of the cervical spine, so there are a plate and screws in his C-spine. He has no other risks for infection or trauma.

He has a CT that demonstrated a large paraspinal abscess and epidural abscess from C3 to T1. And gas in the spinal cord, aka pneumorrhachia, a word I never knew existed. He has no neurologic symptoms of focal infection or meningitis.

Most of the cases of pneumorrhachia follow trauma or epidural injections. Much to my surprise, there is only one case of pneumorrhachia with epidural abscess from S. aureus and two from meningitis, one each from E. coli and Citrobacter

I say surprise given how often I see a whiff of gas from all manner of microorganisms. There are some fun studies on bacterial gas production from both 1930 and 1895, but why a paper from 1895 is still behind a paywall eludes me.

My patient grew S. aureus, although there is not a good reason for the infection. Why S. aureus makes gas and under what circumstances I cannot find. The most impressive gas-forming infection I have seen was a S. aureus pelvic infection.

Now it is debridement and antibiotics and he did just fine.

Rationalization

Rev Med Chil. 2014 Aug;142(8):1061–4. [Pneumorrhachis, spondylitis and meningitis secondary to emphysematous cystitis. Report of one case].

http://www.ncbi.nlm.nih.gov/pubmed/25424679

Diagn Microbiol Infect Dis. 2013 Dec;77(4):370–2. doi: 10.1016/j.diagmicrobio.2013.08.017. Epub 2013 Sep 26. Pneumorachis associated with multiorgan infection due to Citrobacter koseri.

http://www.ncbi.nlm.nih.gov/pubmed/24075632

Intraspinal Air: A CT Finding of Epidural Abscess.

http://www.ajronline.org/doi/pdf/10.2214/ajr.151.6.1217

Spontaneous Pneumorrhachis and Transverse Myelitis Complicating Purulent Meningitis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958990

Pathogenesis, diagnosis and management of pneumorrhachis.

http://link.springer.com/article/10.1007/s00586–006–0160–6

Biochem J. 1930; 24(2): 529–548. PMCID: PMC1254451 Studies in gas production by bacteria Denitrification and bacterial growth phases

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1254451/

A STUDY OF SOME GAS-PRODUCING BACTERIA. A. A. Bennett , E. E. Pammel J. Am. Chem. Soc., 1896,

http://pubs.acs.org/doi/abs/10.1021/ja02088a006

Chapter Sixty-Seven

I Just Want to Giggle

Apr 3, 2015

I am asked to see a patient who has been ill since October. He has had a cough, arthralgias, fatigue and mediastinal lymphadenopathy with a biopsy that showed granulomatous changes but no organism.

An extensive workup by both pulmonary and rheumatology has been negative, and my pre-consult conversation with the pulmonologist revealed no odd exposure history.

Reading the notes and labs before the clinic visit, I note he had been born in Indiana.

Ding Ding Ding.

When I walk into the room, both the patient and his wife are decked out in Notre Dame University paraphernalia. I knew what this was going to be, and I want to go right to the diagnosis, but I force myself to go through the routine.

So aggravating. I want dessert, but habit makes me take the usual H&P to be complete.

It turns out the illness started a few weeks after their marriage in rural Indiana at a day camp. The exam shows splenomegaly.

At this point, I really want to giggle with glee. It is textbook Histoplasmosis. It can’t be anything else. Well, it could, but there are no other risks, and the case is so textbook. It is so rare that the patient reads the textbook. I half expected someone to enter the room to tell me it was all part of a test to see if I could recognize Histoplasmosis.

I usually wait until I have a microbiologic diagnosis before I write these posts, but really. It is either Histoplasmosis or some other process that is exactly mimicking Histoplasmosis. Which would be Histoplasmosis.

I have sent the urine antigen and serology (they were positive) and have asked pathology to re-review the slides to find me the Histoplasma that HAS to be there. It was. Budding yeast were seen on the retrospectroscope.

And I still want to giggle with glee.

Rationalization

Medicine (Baltimore). 1997 Sep;76(5):33954. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature.

https://pubmed.ncbi.nlm.nih.gov/9352737/

MMWR Morb Mortal Wkly Rep. 2012 Sep 21;61:7478. Histoplasmosis outbreak among day camp attendees Nebraska, June 2012.

http://www.ncbi.nlm.nih.gov/pubmed/22992573

POLL RESULTS

When I think I have made an odd diagnosis, I want to

• giggle 9%
• laugh 9%
• titter 9%
• guffaw 18%
• hoot 27%
• Other Answers 27%
  • twist and shout
  • Smirk
  • evil chuckle and/or rebel yell
  • thump my chest and let out a Tarzan yell.
  • snort, cough, sputter and excuse myself from the room.

Chapter Sixty-Eight

Blue Ink

Apr 6, 2015

I sometimes think that the purpose of third-party payers is to avoid, well, paying the first party. Or am I the second party? I received a letter from Nordian, the Medicare billing company, telling me I would no longer be able to bill unless I filled out some forms.

And they had to be signed with blue ink.

Blue ink.

It is hard enough to find a pen in the hospital anymore with everything computerized, but blue ink? I had no such pen handy and so put off finishing the paperwork. If it hadn’t been for someone reminding me, I would have forgotten all about it and lost Medicare billing for a while. And the person reminding me also couldn’t find a blue ink pen. Next time the paperwork comes due, I suspect it will need to be signed with green glitter ink, and all the i’s will have to be dotted with little hearts. I’ll never get that paperwork done.

I am gone for a week, off to NY, NY for NECSS, so no posts after today until the 15th. Good time to order the Puswhisperer from Amazon to tide you over. Just a pair of curiosities today.

First is a male, quadreparetic for 25 years, who presents with autonomic dysreflexia. It has been a decade since he has needed any medical care. A CT shows L2 looking like it had been hit with a hammer. No reason at all for an infection, the last decubitus was 15 years ago.

So we biopsy the lesion. Fusobacterium. Harrumph. 10 hits on the PubMeds. Nothing to suggest a head and neck source, his teeth are pristine. So odd bug, no reason.

The other is a middle-aged male with a sore throat who presents with fevers, multiple septic joints, septic pulmonary emboli, a large neck abscess, and a clot in the internal jugular. Lemierre’s, right? Fusobacterium should grow.

A review of recent cases identified F. necrophorum as the sole etiologic agent in 81.7% of cases and F. necrophorum in combination with other organisms in 10.1% of cases; in a minority of cases (5.5%), organisms other than F. necrophorum were the only isolates recovered. Organisms isolated from blood cultures have included Fusobacterium nucleatum and unspecified fusobacteria, other anaerobic gram-negative bacilli (usually Bacteroides species), Peptostreptococcus species, various streptococci (viridans streptococci, Streptococcus bovis, Streptococcus milleri, and group B and C β-hemolytic streptococci), and miscellaneous organisms, including Eikenella corrodens, Enterococcus species, Eubacterium species [2], Escherichia coli, lactobacilli, and non–multidrug-resistant methicillin-resistant Staphylococcus aureus.

Nope. S. pyogenes.

Nine hits on PubMed, two in adults.

One would think given the propensity for S. pyogenes to cause sore throats, there would be more cases of Lemierre’s syndrome from that organism. Wonder why. And one of three severe ENT infections from Group A Streptococcus this month.

Patients never seem to bother to read the textbooks prior to admission to know what they are supposed to do.

Rationalization

Diagn Microbiol Infect Dis. 2014 Apr;78(4):491–3. doi: 10.1016/j.diagmicrobio.2013.08.025. Epub 2014 Jan 24. Fusobacterium spondylodiscitis: case report and literature review.

http://www.ncbi.nlm.nih.gov/pubmed/24462349

J Infect. 2005 Aug;51(2):E5–9. Vertebral osteomyelitis due to Fusobacterium species: report of three cases and review of the literature.

http://www.ncbi.nlm.nih.gov/pubmed/16038751

Lancet Infect Dis. 2007 Mar;7(3):233. Lemierre syndrome caused by Streptococcus pyogenes in an elderly man.

http://www.ncbi.nlm.nih.gov/pubmed/17317605

Clin Infect Dis. 2005 Oct 15;41(8):1208–9. Lemierre syndrome caused by Streptococcus pyogenes.

http://www.ncbi.nlm.nih.gov/pubmed/16163643

POLL RESULTS

Medicare contracts should be signed with

• blue ink 2%
• pencil 4%
• blood 39%
• green glitter 6%
• unicorn tears 43%
• Other Answers 6%
  • tension, apprehension, and confusion
  • at least two sober witnesses.
  • rubber stamps

Chapter Sixty-Nine

Lap Dance

Apr 15, 2015

I had a patient, I will call her May Parker, who was May Parker III. The third. Odd. I do not think I have ever known a female who was a third who wasn’t royalty, not that I have ever known any royalty. I suppose that in the old day's females would take their husband's last name, rendering any III or IV designation moot, there is less urge to continue the family name in the female offspring. And would her mother be Junior? Yep. According to what I can find on the web, Junior is genderless, and there are the occasional female Juniors. May Parker Jr, daughter of May Parker Sr.

I had an uncle who had all his dental work in Mexico because it was a fraction of the cost of dental care in the US, and he had no dental insurance. I have had the occasional patient who has traveled overseas to have needed procedures since they could afford, for example, their nephrectomy in India but not the US.

The patient in question had a lap band placed in Central America 5 years ago. It worked, with good weight loss, but he presented recently with a week of severe abdominal pain. He is found to have the band eroding into the stomach, so it is removed. Post-op, he has fevers and leukocytosis, and a CT shows multiple, large fluid collections.

The gram stain shows white cells, but no organisms and nothing is growing, so they call me.

I send the fluid for AFB cultures. Why? Because I remembered the following.

Atypical mycobacteria are a problem after cosmetic surgery performed south of the border:

In April 2004, CDC received reports of infections caused by rapidly growing mycobacteria in patients who had undergone cosmetic surgery procedures in Santo Domingo, Dominican Republic.

and rapid growing AFB, in particular, are reported with lap bands:

We report 18 cases of infection associated with laparoscopic gastric banding caused by Mycobacterium fortuitum and M. abscessus in Australia during 2005–2011. We identified cases by reviewing positive cultures at the Queensland state reference laboratory or through correspondence with clinicians, and we obtained clinical and epidemiologic data. Eleven cases of M. fortuitum and 7 cases of M. abscessus infection were identified. The port was thought to be the primary site of infection in 10 of these cases. Complications included peritonitis, band erosion, and chronic ulceration at the port site. Rapidly growing mycobacteria can infect both port and band and can occur as either an early perioperative or late infection.

I was expecting M. fortuitum, but instead, M. abscessus grew. There are other cases like mine in the literature, and I find the long delay from banding to presentation common:

A 34-year-old woman developed insidiously progressing abdominal distension over a period of 1 year associated with abdominal pain, fatigue, night sweating and anorexia 4 years after laparoscopic gastric banding for obesity. Investigation revealed significant ascites with caseating granuloma in peritoneal biopsies from which M. abscessus was isolated. Band erosion with infection and multiple abdominal adhesions were confirmed during laparoscopic removal of the gastric band.

Susceptibilities are pending, but he is much better on clarithromycin and ciprofloxacin. Imipenem and tigecycline are often used to treat M. abscessus, but he has made so much improvement on po it is hard to justify a change to IV pending final cultures.

Rationalization

Mycobacterium abscessus peritonitis associated with laparoscopic gastric banding.

http://www.biomedcentral.com/1471–2334/13/323

Rapidly Growing Mycobacteria Associated with Laparoscopic Gastric Banding, Australia, 2005–2011.

http://wwwnc.cdc.gov/eid/article/20/10/14–0077\_intro

Brief Report: Nontuberculous Mycobacterial Infections After Cosmetic Surgery — Santo Domingo, Dominican Republic, 2003–2004.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5323a4.htm

Chapter Seventy

Known Unknowns

Apr 17, 2015

There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don’t know. But there are also unknown unknowns. There are things we don’t know we don’t know.

Donald Rumsfeld

I do like that quote as it encapsulates medicine so well. I know a little. What I don’t know is enormous. And there are those topics I know I don’t know. Diseases I have read about, rare and unusual, that I do not expect to see ever, or, at most at least once in a career.

And for diseases that I know I don’t know and for what I don’t know, I don’t know, I have PubMed and Google. Having the world's knowledge at my fingertips and constantly searching the web slowly increases my known knowns.

The patient is an elderly female admitted with confusion. Work-up shows she is currently suffering from a case of thoracic shingles that started a week prior to admission, but otherwise, past medical history is negative except for CLL.

MRI is negative, and the LP has a little increase in protein and 300 WBCs. The VZV PCR is negative, as is the rest of her evaluation for an etiology of her encephalopathy. So they call me.

One of my known unknowns is VZV vasculitis. I remembered that VZV could cause a granulomatous angiitis of the carotids, but that was the extent of my knowledge. I had never needed to consider VZV vasculitis before in a differential. So off to the Googles and what do you know. I think she has VZV vasculitis.

We did an MRI, and it was consistent with vasculitis, and she slowly improved on acyclovir. The CSF PCR is usually negative with VZV vasculitis, and the CSF IgG is the test to get. It is pending, but with CLL I have to wonder about its reliability.

It is an interesting manifestation of VZV with lots of variations: large vessels, small vessels, strokes, and bleeds. Manifestations of VZV from the reference in the rationalization, well worth a read:

• Unifocal or multifocal
• Deep-seated infarction more common than superficial infarction
• White matter more commonly affected than grey matter
• Grey–white matter junctions commonly affected
• Involvement of large or small arteries, but more commonly both
• Rash not required for diagnosis
• CSF pleocytosis can include increased red blood cells
• CSF pleocytosis absent in a third of cases
• Detection of VZV antibody superior to that of VZV DNA for diagnosis
• Can cause spinal-cord infarction
• Can cause aneurysm
• Might present with subarachnoid haemorrhage
• Might present with cerebral haemorrhage
• Might present with carotid dissection
• Might cause peripheral arterial disease

and we probably need to consider it more often as a cause of otherwise unexplained neurologic disease.

Rationalization

Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814602/

Chapter Seventy-One

Chicken and Egg

Apr 21, 2015

I try and remember that not every presentation has an infectious disease. Sometimes the cause is, unfortunately, not an infection. My urge is to jump to the infectious diagnosis, and it takes deliberate effort to consider other etiologies.

One of my blind spots is crystalline arthropathies. I have to make a mental effort to consider gout and pseudogout is a reason for a red, hot, swollen, painful joint. Years ago, I had a patient with a polyarticular small joint arthritis I thought for sure was parvovirus. My resident, smarter than me, sent crystals. Gout.

Patient one had a rotator cuff repair several weeks ago and presented with a red hot swollen shoulder. The tap had pseudogout crystals, no organisms, and grew a Coagulase-negative Staphylococcus.

The shoulder was arthroscopically debrided, and all the cultures again grew coagulase-negative Staphylococcus. So it was infection leading to pseudogout? Or pseudogout leading to infection?

This patient’s clinical course was consistent with the possibility that enzymes, released during the early septic process, digested cartilage matrix, releasing, into the joint space, crystals that had been deposited previously in a protected intracartilagenous site.

The second case is a renal transplant patient presenting with sepsis and a red, hot, painful shoulder. Everything grows Group B Streptococcus. And pseudogout crystals in the shoulder as well.

So it was infection leading to pseudogout? Or pseudogout leading to infection?

This sequence was demonstrated in a rat air pouch model of synovium, in which CPPD crystals embedded in facsimile synovial tissue were released after injection of pyogenic bacteria. Coexisting septic arthritis should always be considered when crystals are identified in inflamed joints, particularly in elderly patients with concurrent infections.

There are a smattering of other cases of infection and pseudogout coexisting in the same patient with a hodgepodge of organisms. However, it is rare enough that the chicken and egg question is not asked.

I usually think of gout as a predisposing condition for a septic joint. What little data there is suggests infection sets up the joint for pseudogout. But the literature is sparse enough I can’t say for sure. Part of what needs to be done is to look for crystals in all infected joints rather than infection in all crystalline arthropathies as is usually done.

Of the 265 joint aspirates containing crystals, 183 (69.0%) contained gout crystals, 81 (30.6%) contained pseudogout crystals, and 1 (0.4%) contained both. Four (1.5%) of the aspirates had positive cultures. The mean synovial WBC of the 4 samples with concomitant crystals and septic arthritis was 113,000 (95% confidence interval [CI] 72,700–153,200), which was significantly higher than the entire population at 23,200 (95% CI 19,400–27,000; p < 0.01). Of note, all 4 patients with concomitant disease had significant co-morbidities and synovial WBC counts greater than 50,000. Septic arthritis and acute crystal-induced arthritis can occur simultaneously; there were 4 cases (1.5%) of concomitant disease in our study population. The presence of crystals cannot exclude septic arthritis with certainty.

Rationalization

Septic arthritis, gout, pseudogout and osteoarthritis in the knee of a patient with multiple myeloma.

http://onlinelibrary.wiley.com/doi/10.1002/art.1780150112/abstract.

Aust N Z J Med. 1986 Jun;16(3):336–40.

Crystal shedding in septic arthritis: case reports and in vivo evidence in an animal model.

http://www.ncbi.nlm.nih.gov/pubmed/3465309

J Emerg Med. 2007 Jan;32(1):23–6. Does the presence of crystal arthritis rule out septic arthritis?

http://www.ncbi.nlm.nih.gov/pubmed/17239729

Chapter Seventy-Two

Medications, Medications, Medications

Apr 22, 2015

I have a patient I have had on a long course of doxycycline and levofloxacin for Nocardia. After nine months, her brain and lung abscesses are finally gone. Cure. So nice.

But in the last month, she has had some side effects to his antibiotics. Although her antibiotics are dosed for renal failure, since I can’t do drug levels, there is the real possibility that there is drug accumulation leading to toxicity.

First is a blistering rash on her hands and neck. This, I suspect, is photosensitivity from the doxycycline. We have actually had sunshine the last week, and the rash is in sun-exposed areas.

But the rash looks more like the cases of porphyria cutanea tarda I have seen. I totally missed a case of porphyria cutanea tarda in an AIDS patient early in my career, and my failures have always made more of an impression than my successes. There are 3 case reports of quinolones causing pseudoporphyria. So maybe it is the levofloxacin.

Also, all her nails are blue and separating from the finger, and there is a bit of blue on the tip of her nose. It is more of a robin egg blue, and she is not on silver. Tetracyclines can cause black nails, so I suspect this may also be from the levofloxacin. The closest I can get is sparfloxacin for the blue nails and levofloxacin, causing blue skin. Both drugs may cause onycholysis.

Photo-onycholysis is a phototoxic reaction, which is usually drug-induced. It consists of the separation of the nail from the nail bed due to ultraviolet radiation. We report two cases of female patients who developed distal onycholysis while receiving doxycycline. Among the drugs that cause photo-onycholysis, the most frequently cited are tetracyclines, psoralens and fluoroquinolones.

Finally, she has been having hypnagogia, intense hallucinations upon awaking from sleep that seems real. I had one about a year ago, convinced there was a man at the foot of the bed when I awoke in the middle of the night. Scared the crap out of me, it seemed so real. She sees people and giant bugs that also seem very real.

Neither of the antibiotics are associated with hypnagogia per se, but there is no shortage of reports of quinolones causing visual hallucinations. So why not hypnogogic hallucinations?

Now that the Nocardia is gone, I can stop the antibiotics, and hopefully, the nails, the blue, and the waking dreams will fade.

They did.

Rationalization

Clin Exp Dermatol. 2008 Jan;33(1):109–10. Epub 2007 Nov 15. Pseudoporphyria occurring during a course of ciprofloxacin.

http://www.ncbi.nlm.nih.gov/pubmed/18021274

Indian J Dermatol Venereol Leprol. 2005 Jan-Feb;71(1):47–9. Sparfloxacin induced blue/black discoloration of all nails: report of three cases.

http://www.ncbi.nlm.nih.gov/pubmed/16394365

Acta Dermatovenerol Alp Pannonica Adriat. 2004 Dec;13(4):135–6. Photo-onycholysis: two cases induced by doxycycline.

http://www.ncbi.nlm.nih.gov/pubmed/15818449

Blue-Gray Pigmentation in Trunk and Extremities in a 71-Year-Old Man.

http://archderm.jamanetwork.com/article.aspx?articleid=1708454

Arch Soc Esp Oftalmol. 2007 May;82(5):299–301. [Visual hallucinations secondary to ciprofloxacin treatment].

http://www.ncbi.nlm.nih.gov/pubmed/17516267

POLL RESULTS

The usual cause of new signs and symptoms is

• drugs 14%
• medications 27%
• pills 2%
• nostrums 11%
• pharmaceuticals 30%
• Other Answers 16%
  • dogs
  • All of the above
  • iatrogenic
  • Television
  • Web-MD
  • Crystal Meth
  • more astute observation of the subject.

Chapter Seventy-Three

Appy

Apr 24, 2015

I am an adult ID doc. It is who I treat, not how I might behave outside the hospital. You are only young once, but you can be immature all your life. But I do not often take care of diseases that occur mostly in children.

The patient is in his mid–40’s and presents with abdominal pain. He has been undergoing consolidative chemotherapy (not neutropenia inducing) but has no other medical problems.

CT of the abdomen shows phlegmon and multiple small abscesses from a ruptured appendix.

I used to think that appendicitis was a reason for surgery. Not anymore. In the pediatric literature, medical and surgical have mostly the same outcomes. Sure surprises me.

Even a perforated appy can be treated with antibiotics and percutaneous drainage:

The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon.

And it may be better to wait:

Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3; CI: 1.9–5.6; P < 0.001).

Perhaps there should be an interval appendectomy after the patient is all better. Some suggest it

On the other hand, 84% of patients had persistent acute appendicitis, chronic appendicitis, evidence of inflammatory bowel disease, or neoplasm identified, and likely benefited from surgical appendectomy.

CONCLUSIONS:

Interval appendectomy provides diagnostic and therapeutic benefit to patients who present with a right lower quadrant abdominal inflammatory focus, and should be carefully considered in all adult patients.

and

After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6–1.7) and an important benign disease in 0.7% (CI: 0.2–11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7–11.1).

Some do not:

Most patients with acute appendicitis undergo appendectomy initially. For those treated nonoperatively, the recurrence rate is low. Routine IA after initial successful nonoperative treatment is not justified and should be abandoned

And when you think about it, what is appendicitis but a subset of diverticulitis? And most of the time, diverticulitis doesn’t need surgery.

And what is the reason for appendicitis? Maybe it is a Fusobacterium infection. There is a curious literature to suggest that the majority of acute appendicitis is due to Fusobacterium invasion of the wall, even of the pus and lumen will grow a hodgepodge of bowel bacteria.

Fusobacteria (mainly Fusobacterium nucleatum and necrophorum) were a specific component of these epithelial and submucosal infiltrates in 62% of patients with proven appendicitis. The presence of Fusobacteria in mucosal lesions correlated positively with the severity of the appendicitis and was completely absent in caecal biopsies from healthy and disease controls. Main faecal microbiota represented by Bacteroides, Eubacterium rectale (Clostridium group XIVa), Faecalibacterium prausnitzii groups and Akkermansia muciniphila were inversely related to the severity of the disease.

If so, it should better with antibiotics. It is not hard to kill a Fusobacterium. So maybe it is not the fecalith after all that causes the appy to go bad.

Rationalization

Am Surg. 2015 Mar;81(3):297–9. Pathologic Findings Suggest Long-term Abnormality after Conservative Management of Complex Acute Appendicitis.

http://www.ncbi.nlm.nih.gov/pubmed/25760207

J Surg Res. 2010 Nov;164(1):91–4. doi: 10.1016/j.jss.2009.05.025. Epub 2009 Jun 16. Can interval appendectomy be justified following conservative treatment of perforated acute appendicitis?

https://pubmed.ncbi.nlm.nih.gov/19691990/

J Pediatr Surg. 2010 Jan;45(1):236–40. doi: 10.1016/j.jpedsurg.2009.10.039. Initial laparoscopic appendectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial.

http://www.ncbi.nlm.nih.gov/pubmed/20105610

Arch Surg. 2005 Sep;140(9):897–901. Routine interval appendectomy is not justified after initial nonoperative treatment of acute appendicitis.

http://www.ncbi.nlm.nih.gov/pubmed/16175691

Ann Surg. 2007 Nov;246(5):741–8. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/17968164

Gut. 2011 Jan;60(1):34–40. doi: 10.1136/gut.2009.191320. Epub 2009 Nov 18. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum.

http://www.ncbi.nlm.nih.gov/pubmed/19926616

Chirurgia (Bucur). 2012 Nov-Dec;107(6):756-60. The importance of fecaliths in the aetiology of acute appendicitis.

http://www.ncbi.nlm.nih.gov/pubmed/23294954

Chapter Seventy-Four

Something Parasitic This Way Comes

May 1, 2015

You may not know it, but part of the testing for blood donors now includes Chagas (Trypanosoma cruzi) serology. It is rare in US donors to have a positive:

A total of 299,398 donors were queried; 23,978 at-risk and 25,587 control donations were tested, and T. cruzi antibodies were confirmed in 34 donors (33 and 1, respectively).

But rare things occur, and I have my first. She is seropositive, but no cardiac or GI symptoms.

The patient is from a more typical risk area, S. America, where it can be found in 9000-year-old mummies. You might think of Chagas as a disease of immigrants.

Chagas disease causes the highest burden of any parasitic disease in the Western hemisphere. By applying published seroprevalence figures to immigrant populations, we estimate that 300,167 individuals with Trypanosoma cruzi infection live in the United States, with 30,000–45,000 cardiomyopathy cases and 63–315 congenital infections annually. T. cruzi causes a substantial disease burden in the United States.

But Chagas is found all throughout the bottom half of the US and is probably under-recognized by those at risk and those treating patients. Hunters and perhaps the homeless may be most at risk.

While we are still in the process of enrollment, we were astonished by the higher than expected percentage (6/17; 36%) of people who acquired their infection here in the US as opposed to a Chagas endemic Latin American country. Interestingly, most (67%) of these individuals reported an extensive history (10+ years) of hunting or camping activities, leading us to speculate that time outdoors in rural settings could place individuals at higher risk for infection.

With dogs being a reservoir.

The CDC has confirmed the diagnosis and they are the only ones with benznidazole as part of investigational protocols. I look forward to the paperwork. Sigh.

Benznidazole appears to have modest efficacy:

Compared with no treatment, benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure.

And lots of toxicity, especially neuropathy and angioedema. But it is all we have.

Here in the great Pacific NW, I do not expect to see another case, but you all in the South will probably have more experience in the future. Although the disease may come North with global warming,

Expected distributional shifts of vector species due to climate change are likely to alter spatial patterns of risk of Chagas disease, presumably through northward expansion of high-risk areas in North America.

But by that time, I will likely be dead.

Rationalization

Blood Screening FAQs

http://www.cdc.gov/parasites/chagas/gen\_info/screening.html

An Estimate of the Burden of Chagas Disease in the United States

http://cid.oxfordjournals.org/content/49/5/e52.short

Seroepidemiology of Trypanosoma cruzi, Etiologic Agent of Chagas’ Disease, in US Blood Donors

http://jid.oxfordjournals.org/content/176/4/1047.short

A 9,000-year record of Chagas’ disease

http://www.pnas.org/content/101/7/2034.short

Parasit Vectors. 2015 Apr 1;8:197. doi: 10.1186/s13071–015–0815–4. Knowledge, attitudes, and practices of Texas hunters: a potentially high-risk population for exposure to the parasite that causes Chagas disease.

http://www.ncbi.nlm.nih.gov/pubmed/25886035

Potential novel risk factors for autochthonous and sylvatic transmission of human Chagas disease in the United States.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094476/

Distribution and characterization of canine Chagas disease in Texas.

http://www.sciencedirect.com/science/article/pii/S0304401707006711

Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.

http://www.ncbi.nlm.nih.gov/pubmed/?term=16702588

Clin Infect Dis. 2015 Mar 24. pii: civ230. High Frequency of Adverse Reactions and Discontinuation With Benznidazole Treatment for Chronic Chagas Disease in Milan, Italy.

http://www.ncbi.nlm.nih.gov/pubmed/25805302

Projected Future Distributions of Vectors of Trypanosoma cruzi in North America under Climate Change Scenarios.

http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002818

POLL RESULTS

With global warming I most fear

• Chagas 3%
• Drought 33%
• An increase in deodorant Failures 15%
• having to change to a Prius. Ew. 3%
• Air conditioning costs 18%
• Other Answers 27%
  • widespread displacement of coastal populations
  • Lousy skiing
  • New brands of cooties.
  • Extinction
  • living long enough to watch it all fall apart.
  • It's global climate evolution. Climate temperature changes have been happening for centuries. This is just another blip on the ever changing weather radar on the earth's long, evolving weather history
  • the return of Godzilla from Monster Island where he has been vacationing these past few decades.
  • everyone going topless

Chapter Seventy-Five

Going Clubbing

May 4, 2015

The physical exam is usually not that helpful. Occasionally you come across some pathology that is interesting, but in my world, most of the diagnoses come from history and labs, usually the cultures. Endocarditis is one of those rare diseases where the exam is helpful.

Like this case. She has been ill for at least three months. In May, she had been in Outside Hospital with confusion and fever, and S. sanguis grew in the blood cultures. For reasons I do not know, the treating physicians did no realize that a S. sanguis bacteremia on two separate days is endocarditis and not a primary bacteremia from poor dentition, even if the ECHO is negative, which it was. She was treated with a course of po amoxicillin and transiently improved.

Fast forward two months. Same presentation: fevers and S. sanguis in the blood this time, a different physician cares for the patient and recognizes the diagnosis, especially now that the feet have numerous classic emboli.

The patient has the endocarditis triad: a changing murmur, emboli (I find a few in the conjunctiva as well), and positive blood cultures.

And she has clubbing. I have never seen clubbing in endocarditis, probably as I have never had a patient go undiagnosed with endocarditis for quite this long.

The only other case of clubbing I have been the first to notice is a patient who had recurrent pneumonia but, in fact, had an underlying lung cancer, which accounts for 90% of clubbing.

Among the different types of thoracic malignancy, lung cancer is responsible for 80% cases of clubbing, whereas pleural tumors and other intrathoracic and mediastinal growth contribute to 10% and 5% cases, respectively. On the other hand, the prevalence of clubbing in lung cancer patients ranges from 5% to 15%.

There is a large differential for clubbing, although I find no other reason besides endocarditis by history or the usual admitting tests,

infective endocarditis usually causes a milder form of clubbing,

In a study out of India, clubbing was seen in 58% of patients. I look at every patient’s nails and I never find clubbing, in endocarditis or other diseases, although I rarely take care of lung cancer patients in the erythropoietin era.

Clubbing may regress with cure of the endocarditis:

A patient with a corrected coarctation of the aorta subsequently developed infective endocarditis on a congenital bicuspid aortic valve. Resolution of the radiographic bone changes of hypertrophic pulmonary osteoarthropathy was demonstrated following treatment of the infection.

Clubbing

was first described by Hippocrates nearly 2500 years ago in a patient with empyema. Because of this, it is often described as Hippocratic finger and is regarded to be the oldest sign in clinical medicine.

His was in a patient with chronic empyema. Hippocrates wrote:

“The nails of the hand are bent; the fingers are hot, especially in their extremities.”

It may be the oldest finding, but there are only 41 hits on Pubmed for endocarditis and clubbing. As to the pathophysiology, I’ll let you read the Medscape review. How much of the physiology applies to the finding in endocarditis, I do not know, but I like the quote

Clubbing is one of those phenomena with which we are all so familiar that we appear to know more about it than we really do.

Me? I don't know all that much. But it is a cool finding.

Rationalization

Lung India. 2012 Oct-Dec; 29(4): 354–362. doi: 10.4103/0970–2113.102824 PMCID: PMC3519022 Digital clubbing http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519022/

Ir J Med Sci. 2009 Sep;178(3):351–3. doi: 10.1007/s11845–008–0231–2. Epub 2008 Oct 9. Postoperative regression of clubbing at an unexpected rate in a patient with aortic and mitral valve replacement due to infective endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/18843516

Int J Cardiol. 2005 Feb 15;98(2):253–60. Characteristics of infective endocarditis in a developing country-clinical profile and outcome in 192 Indian patients, 1992–2001

http://www.ncbi.nlm.nih.gov/pubmed/15686775

Postgrad Med J. 1980 Jul;56(657):513–5. The resolution of hypertrophic pulmonary osteoarthropathy following treatment of subacute infective endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/7443609

Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.

http://www.ncbi.nlm.nih.gov/books/NBK366/

Pathophysiology.

http://emedicine.medscape.com/article/1105946-overviewa0104

Chapter Seventy-Six

Image

May 7, 2015

This is mostly an infectious disease blog, but occasionally I like to wander off and whinge about aspects of medicine that annoy me. But I can still tie in infections to ANYTHING.

I don’t watch medical shows on TV. They irritate me too much. I found House unwatchable from a medical point of view, even though I love Hugh Laurie and remain of the opinion that Blackadder was one of the great comedies of all time. The one House I saw concerned a patient with rabies. I beat House to the diagnosis (much to the irritation by my children) and his management of the case before the diagnosis was, as I remember it, truly awful.

The only TV show I ever thought got medicine right was Scrubs, despite the CXR being up backward in the opening credits. Probably a case of situs inversus. My wife, an NP, thinks that nursing is also portrayed horribly in the media. I would suspect that no profession is happy with their portrayal on TV.

Stereotypes annoy me as well. Like the Skeptical Inquirer covers. What does a doctor look like?

Whitecoat? Check.

I practice in the West, and we are a bit more casual, and many no longer wear white coats. I am against white coats as they get dirty and could be an infection source:

Although most of the white coats had been washed within the past 2 weeks, the sides of the coats were the most highly contaminated areas followed closely by the collar and pockets. Staphylococcus aureus was the most common isolate followed by coagulase-negative Staphylococci and Gram-negative non fermentors. Most of the Gram-positive cocci were resistant to Penicillin, Erythromycin and Clindamycin.

Our house staff are no longer given a white coat.

Not all agree, getting rid of white coats is worth it:

The introduction of ‘bare below the elbows’ policies to facilitate handwashing led to the disappearance of the white coat from medical and surgical wards. While rates of key healthcare acquired infections in hospitals, e.g. Clostridium difficile and methicillin-resistant Staphylococcus aureus bacteraemia, have fallen, argument continues around the contribution of hand hygiene and dress codes to these changes. Conversely, the number of complaints against clinicians continues to rise, and respect for medical staff is falling. Are these phenomena linked to the disappearance of the white coat?

and

patients prefer white coats, and they contribute to greater comfort and confidence in their physicians, despite knowledge of theoretic concerns of disease transmission.

Oddly, I would place infection control ahead of style and ban white coats. Ties as well:

This study is a prospective, controlled investigation of the effect of shirt sleeves and ties on the transmission of bacteria from doctors to patients. Results show that wearing an unsecured tie results in greater transmission, but that sleeve length does not affect transmission rate.

and the male doctor is, of course, wearing a tie.

And the stethoscope. No competent self-respecting doctor who uses a stethoscope for anything besides a fashion accessory would use the ones around their neck. Those cheap ass scopes hurt to use and are worthless for a careful exam. I know. Big deal. It is the kind of detail that annoys me.

But more than anything, it is the glasses. Big, black, nerd glasses. Maybe it is an East coast thing, but I know no one who wears those glasses. Not even hipsters. And I would bet good money that there is no glass in the female's frames.

And, like everything in medicine, glasses are only a risk for infection:

Of 20 eyeglasses, 19 were contaminated with Staphylococcus epidermidis (3 of them additionally grew S haemolyticus or S xylosus), and the remaining one grew S aureus.

I am certainly not a sartorial role model, but these kinds of cliches are an irritation. Of course, if the media presented doctors as they really looked, well, I suppose a cliche is better than reality. And if we wanted to optimize dress to minimize infection, perhaps the hospital would be more like the ancient Olympics. And no one wants that.

Rationalization

J Clin Diagn Res. 2012 Oct;6(8):1381–4. doi: 10.7860/JCDR/2012/4286.2364. White coats as a vehicle for bacterial dissemination.

http://www.ncbi.nlm.nih.gov/pubmed/23205352

J R Coll Physicians Edinb. 2014;44(4):293–8. doi: 10.4997/JRCPE.2014.410. Changes to clinician attire have done more harm than good.

http://www.ncbi.nlm.nih.gov/pubmed/25516900

Ochsner J. 2013 Fall;13(3):334–42. Patient Preferences for Doctor Attire: The White Coat’s Place in the Medical Profession.

http://www.ncbi.nlm.nih.gov/pubmed/24052762

J Hosp Infect. 2012 Mar;80(3):252–4. doi: 10.1016/j.jhin.2011.12.012. Epub 2012 Feb 2. Prospective study on the effect of shirt sleeves and ties on the transmission of bacteria to patients.

http://www.ncbi.nlm.nih.gov/pubmed/22305288

J Orthop Surg (Hong Kong). 2012 Apr;20(1):75–7. Infection risk from surgeons’ eyeglasses.

http://www.ncbi.nlm.nih.gov/pubmed/22535816

Skeptical Inquirer — Volume 39.3

http://www.csicop.org/si/archive/category/volume\_39.3

Skeptical Inquirer — Volume 38.6

http://www.csicop.org/si/archive/category/volume\_38.6

POLL RESULTS

The best depiction of doctors is found in

• Scrubs 22%
• MASH 16%
• Marcus Welby 3%
• ER 26%
• Star Trek 21%
• Other Answers 12%
  • st elsewhere
  • ST Elsewhere
  • House. Not really.
  • knick
  • house md

Chapter Seventy-Seven

Time for a fish boil.

May 8, 2015

The patient is an elderly female on methotrexate for rheumatoid arthritis, who presents with a cluster of nodules on the calf. They do not get better and are eventually biopsied.

They grow M. marinum, the cause of aquarium granuloma. And she does have an aquarium that she maintains. The thing is, she doesn’t maintain it with her legs. It is not like she is making fish wine, marching up and down on the fish.

I asked seven ways to Sunday about any way for the fish tank water to get to her calf, but she could not remember any. Nor is there any other water exposure to account for the infection.

So I wonder. Just what is the source of M. marinum, the fish, or the water?

The source might be water, although it may depend on the water. M. marinum is found in Romanian and Iraqi tap water.

The sources of MOTT (Mycobacterium Other Than Tuberculosis) were tap water and dust. The most frequent species was Mycobacterium marinum

and

The 252 isolates were identified as M. avium complex (21), M. marinum (15), M. kansasii (30), M. simiae (20), M. szulgai (19), M. xenopi (16), M. malmoense (11), M. fortuitum (37), M. chelonae (50) and M. abscessus (33).

It is suggested that chlorination has led to the disappearance of M. marinum as a cause of swimming pool granuloma and why it tends to be seen with aquariums.

But it looks like it is the fish that are the vector for the infection.

A survey was carried out on occurrence of Mycobacterium marinum in fish kept in aquaria and those living in their natural environment. Species-specific qPCR targeting the erp and IS2404 genes together with the conventional culture method were used. The analysis of 72 ornamental fish (n = 216 samples: gills, muscle and intestine) collected from aquaria revealed the presence of M. marinum in 30 individuals (41.7%) of whom 17 (23.6%) were later culture positive. Culture-independent detection revealed the presence of M. marinum in 16 of 83 environmental samples (19.3%) collected in aquaria.

and it is not just M. marinum:

387 fish were examined and Mycobacterium spp. were isolated from 181 (46.8%) fish. In the second survey 127 batches of ornamental fish from different countries were examined. Mycobacterium spp. were isolated from 38 (29.9%) batches. The following species were found: M. fortuitum, M. peregrinum, M. chelonae, M. abscessus, M. marinum, M. gordonae, M. nonchromogenicum and M. interjectum. There was a high prevalence of infection independent of the presence of macroscopic lesions. Mycobacterium fortuitum and M. chelonae were more prevalent than M. marinum in the samples examined.

and in Canada

The presence of M. marinum was proven in the aquarium environments of two patients. Although M. marinum is described as being present in water, it was detected only in fish.

It seems time for a fish boil. It is also called Fish gambler’s tenosynovitis, from betting over fighting fish and, I suppose, dispatching the loser. It seems a more inane way than usual to throw away your money. Next up: betting on paint drying.

I assume she scratched her calf shortly after having her hands in the tank and inoculated herself.

There are only a few reports of M. marinum infections in patients receiving various immunosuppressants, and they do worser. It appears to be steroids and methotrexate, that is the gruesome twosome. She was getting much better on minocycline when I saw her, so we stayed the course.

Rationalization

Bacteriol Virusol Parazitol Epidemiol. 1998 Oct-Dec;43(4):229–35. Nontuberculous mycobacteria in the hospital environment

https://www.ncbi.nlm.nih.gov/pubmed/10422317

J Fish Dis. 2014 Jun;37(6):527–33. doi: 10.1111/jfd.12135. Epub 2013 Aug 16. Relative prevalence of Mycobacterium marinum in fish collected from aquaria and natural freshwaters in central Europe.

https://www.ncbi.nlm.nih.gov/pubmed/23952681

Can J Microbiol. 2012 Jan;58(1):39–44. doi: 10.1139/W11–104. Epub 2011 Dec 19. Mycobacterium marinum infections in humans and tracing of its possible environmental sources.

https://www.ncbi.nlm.nih.gov/pubmed/22182182

J Fish Dis. 2008 Jun;31(6):433–41. doi: 10.1111/j.1365–2761.2008.00924.x. Occurrence of Mycobacterium spp. in ornamental fish in Italy.

http://www.ncbi.nlm.nih.gov/pubmed/18471099

Diagn Microbiol Infect Dis. 2007 Oct;59(2):227–30. Epub 2007 Jun 15. Fish gambler’s tenosynovitis caused by Mycobacterium marinum: environmental investigation of a fishing pond in Southern Taiwan.

http://www.ncbi.nlm.nih.gov/pubmed/17572037

Chapter Seventy-Eight

Another Rash I Do Not Recognize

May 11, 2015

I hate rashes, mostly because I am not good at visuals. In med school, histology almost did me in. All I saw was purple and red on the slides. I could never figure out the portal triad. It is why I rely on the history to make a diagnosis. I am much more verbally oriented.

The patient is a middle-aged male, just back from a vacation in the Caribbean, who has a rash.

Not only on the skin, but there was a lesion on the tongue that was ulcerated.

It looked just like this (https://secure2.pbase.com/leobarco/image/69914524). See the picture. Of course, if you look at the picture, you will see the diagnosis. But at the time, it did not look like anything I had seen before, although I will admit I had a nagging feeling I should know the disease.

No fevers. No leukocytosis. No risks for anything I could find. I could not see this as an infection, especially since it involved the tongue. There is one (relatively) common infection that causes tongue ulcers, histoplasmosis, and this was not clinically histoplasmosis.

So dermatology was called, who did a biopsy and confirmed Sweet’s Syndrome, aka Acute Febrile Neutrophilic Dermatosis.

I have seen a few Sweets in my day, but they all looked more like a cellulitis. I have discussed them on this blog before. I thought I wrote about the case of Sweets I saw from G-CSF, but I can’t find it.

Sweet’s is an interesting disease, occurring both after infections and as well as from malignancy, drugs, and pregnancy.

I can only find a few cases of Sweet’s involving the tongue, so that would be the odd part of the presentation. He improved rapidly on a big dose of prednisone. Work up for underlying disease will be done as an outpatient.

Rationalization

J Calif Dent Assoc. 2010 Mar;38(3):193–5.v Lingual ulceration in disseminated histoplasmosis.

http://www.ncbi.nlm.nih.gov/pubmed/20369452

Eur J Dermatol. 1998 Oct-Nov;8(7):503–5. Sweet’s syndrome associated with granulocyte colony-stimulating factor.

http://www.ncbi.nlm.nih.gov/pubmed/9854164

Dermatology. 1995;190(4):335–7. Sweet’s syndrome and acute myelogenous leukemia in a patient who presented with a sudden massive swelling of the tongue.

http://www.ncbi.nlm.nih.gov/pubmed/7655121

Chapter Seventy-Nine

Nailed It

May 13, 2015

As I have said before, as a rule, the physical examination is more for entertainment. It is interesting to find pathology, but it is rare to make a diagnosis based on the physical exam alone as opposed to the history and cultures. At least for me. Your mileage may vary

Part of the problem of the exam is actually seeing what you are examining. It is easy not to note the pathology right in front of you. I have found, for example, the occasional Marfans, first hinted at because of blue sclera. I half wonder how many health care providers looked at the eyes, but for some reason, never saw the blue. I also wonder how often I look at pathology right in front of me and do not see it. It is much easier to note pathology if you are specifically trying to find it—the bane of inattentional blindness, hiding the Gorilla in the CT.

I look at the nails of almost all my patients. Mostly I am looking for embolic events, but occasionally I find pathology in the nails that are indicative of other systemic diseases. I always like to find Beau’s lines; it is kind of like looking at tree rings.

Yesterday I was looking at the hands of a patient with Group B streptococcal bacteremia patient, and the nails were odd.

They were a reversed French Nail. Yes. I know what French nails are. Want to make something of it? The distal third of the nails were red while the proximal 2/3’s were white. Silly me, I thought it was the red that was pathologic, but it is the white part of the nail that was abby normal, a ground glass appearance with no lunula.

The patient said his toe and fingernails had all turned that way about a year and a half ago, and no one could tell him why. I was sure I had never seen anything like it before.

So I went searching the net and quickly found it here: Terry’s nails. Never saw that before. Or had I? According to the Wikipedia

Eighty percent of patients with severe liver disease have Terry’s nails, but they are also found in patients with kidney failure, (and) in patients with congestive heart failure.

It was actually 82% of patients. Terry’s nails are due to decreased vascularity and increased connective tissue under the nail.

But given how common the underlying pathology is, I must have had a patient with Terry’s nails before, I just didn’t see it.

My patient? Cirrhosis from chronic hepatitis C.

I just hope I never have a patient with a case of gorillas. I will certainly miss it.

Addendum

I found out that the scientific name for the Western lowland gorilla is Gorilla gorilla gorilla. I guess the first person to name the animal had been surprised by one. If I were walking through the scrub and stumbled upon a gorilla, I would probably freak and shout, “Gorilla gorilla gorilla.”

Rationalization

Study: Most radiologists don’t notice a gorilla in a CT scan.

http://www.washingtonpost.com/blogs/wonkblog/wp/2013/02/19/study-most-radiologists-dont-notice-a-gorilla-in-a-ct-scan/

Nail Abnormalities: Clues to Systemic Disease.

http://www.aafp.org/afp/2004/0315/p1417.html

Lancet. 1954 Apr 10;266(6815):757–9. White nails in hepatic cirrhosis.

http://www.ncbi.nlm.nih.gov/pubmed/13153107

Am J Med. 2011 Jul;124(7):602–4. doi: 10.1016/j.amjmed.2010.11.033. Terry’s nails: a window to systemic diseases.

http://www.ncbi.nlm.nih.gov/pubmed/21683827 or

http://www.amjmed.com/article/S0002–9343(11)00257–9/fulltext

Terry's nails

https://en.wikipedia.org/wiki/Terry%27s\_nails

Abby Normal

https://www.youtube.com/watch?v=yH97lImrr0Q

POLL RESULTS

I

• look, but do not see 10%
• don't look 2%
• see all, know all 10%
• go through the motions in a distracted daze until sweet death releases me 28%
• used to look, but I can't see a damn thing with these bifocals 48%
• Other Answers 2%
  • wh ere?

Chapter Eighty

Lack a Bacillus? Nope.

May 18, 2015

Any bug can infect any organ given a perfect storm of bad luck. It is what makes ID interesting and drives this blog.

The patient is an elderly male getting his first round of chemo for Hodgkins lymphoma. At baseline, he is not high functioning, and the chemotherapy renders him mostly bed-bound.

He is in the hospital for neutropenic fevers and is placed in standard antibiotics. His fevers persist, and after five days, his normal CXR evolves, with an infiltrate in the LLL. He is has a bronchoscopy, and they call me to fine-tune the antibiotics.

Not much on the exam, the patient by report mostly lies curled in bed and, as such is somewhat of an aspiration risk.

The gram stain is 4+ gram-positive rods, and I am thinking it is going to be a Corynebacterium of some sort. A wide variety of Corynebacterium can cause pneumonia.

Nope.

Lab report says a Lactobacillus.

So I call them. What does the magic machine, aka the MALDI-TOF, say?

99% Lactobacillus rhamnosus.

And there it is on the med list, Lactobacillus rhamnosus, a probiotic to prevent antibiotic-associated diarrhea.

I can’t tell if the Lactobacillus rhamnosus strain from the probiotic and bronchoscopy are the same. Lactobacillus rhamnosus is found in humans, just not one of the more common strains.

I suspect that this is a probiotic aspiration pneumonia, and he did improve on ampicillin, although I do not know if he improved because of the ampicillin as his WBC returned as well.

Every few years, I see an infection from probiotics, usually a bacteremia. I wonder if we will see an increase in reporting of Lactobacillus in pulmonary secretions from aspiration. We are giving more probiotics, and with the new technologies, we can easily identify bacteria that would have been called normal flora and ignored.

Rationalization

J Clin Microbiol. 2014 Aug;52(8):3124–6. doi: 10.1128/JCM.01065–14. Epub 2014 Jun 4. Probiotic-associated aspiration pneumonia due to Lactobacillus rhamnosus.

http://www.ncbi.nlm.nih.gov/pubmed/24899028

Clin Infect Dis. 2004 Jan 1;38(1):62–9. Epub 2003 Dec 4. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG.

http://www.ncbi.nlm.nih.gov/pubmed/14679449

Clin Infect Dis. 2015 May 15;60 Suppl 2:S98-S107. doi: 10.1093/cid/civ072. Lactobacillus species: taxonomic complexity and controversial susceptibilities.

http://www.ncbi.nlm.nih.gov/pubmed/25922408

Antimicrobial susceptibilities of Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use.

http://jac.oxfordjournals.org/content/59/5/900

Chapter Eighty-One

More Fleas and Lice

May 21, 2015

The patient is on high dose prednisone and Rituxan for an autoimmune disease. She comes in with some mild shortness of breath and a CT that has multiple nodules all throughout the lung. They are solid, the biggest about a centimeter, none are cavitary. She has no risk factors by travel etc. for an odd infection.

The bronchoscopy is unimpressive for pus, negative for PJP by DFA, galactomannan, and the more mundane gram stain and culture, so they ask me to weigh in.

I bet cancer or fungus by the look of the CT. They look like hematogenous, not inhalational disease. I figure that the BAL will not be diagnostic and they arranged for percutaneous biopsy of the lesions.

The next day the (1,3)- ß-D-glucan comes back > 500. That narrows the differential.

From the package insert:

The Fungitell ß-D Glucan assay detects (1,3)- ß-D-glucan from the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, and Pneumocystis jiroveci.

The Fungitell ß-D Glucan assay does not detect certain fungal species such as the genus Cryptococcus, which produces very low levels of (1,3)- ß-D-glucan, nor the Zygomycetes, such as Absidia, Mucor, and Rhizopus, which are not known to produce (1,3)- ß-D-glucan. Studies indicate Blastomyces dermatitidis is usually not detected due to little (1,3)- ß-D-glucan produced in the yeast phase.

And, as readers from this blog know, Nocardia.

So based on the negative studies and the CT I bet on Nocardia or Aspergillus despite the negative BAL galactomannan. Interstitial/hematogenous lung infections may not reach the alveoli where the bronchoscopy can find them. Miliary TB, as an example, is isolated less than half-time on bronchoscopy.

Then pathology calls. The BAL is PJP positive by silver stain.

Really? Are you sure? The DFA is negative.

Nope. He showed it around, and it is classic Pneumocystis. So that explains the Fungitel and (in retrospect) the LDH of 400 and the O2 saturation of 92%. Every test has false negatives and false-positives. So the DFA was a false-negative

But the nodules? A quick Pubmed finds PJP causing solitary and multiple nodular granulomas in both HIV and other patients. So it happens; I just had never seen a case.

So I get ready to call the house staff when another pathologist calls.

The nodule? Branching gram-positive rods. Looks like Nocardia. Which would also explain the positive 1–3 beta-D glucan. And the nodules.

While I am at heart an Occam’s kind of guy, my patients remain disciples of Hickam's dictum.

At least everything can be treated with TMP/Sulfa, killing two stones with one bird.

Rationalization

In Medicine You Can Never Know Enough.

http://boards.medscape.com/forums/?128@@.2a791f88!comment=1

Diagnosis and management of miliary tuberculosis: current state and future perspectives.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544391/

Pediatr Nephrol. 2013 Jan;28(1):145–9. doi: 10.1007/s00467–012–2286–6. Epub 2012 Sep 5. Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/22948319

Chapter Eighty-Two

Drugs Don't Stay Put

May 27, 2015

Bad outcomes make an impression. I remember complications and failures far more clearly than my successes.

The patient is an elderly female with a chronic entero-cutaneous fistula and abscess as a complication of a necrotic gallbladder as well as on dialysis from diabetic renal disease. For a variety of reasons, the patient is not a good surgical candidate, so the abscess has had a few drains in it for many weeks.

The abscess was being flushed as an outpatient several times a day with tobramycin containing saline when she was admitted with fevers and an altered mental status.

I was asked to see the patient and noted the aminoglycoside in the flush.

As an intern, I had a patient go deaf from neomycin flushes in a chronic peritoneal abscess, and the neomycin levels were sky-high. The peritoneum and abscess cavity have excellent membranes for drug absorption. In rat drug studies, drugs are given intraperitoneally with excellent blood levels, as it is so hard to get an IV into the arm of a rat. And rats tend to use the lines for IVDA.

So I checked a random tobramycin level, and it was 3.1. Given the renal function of the patient, I think it is probably a steady state rather than a trough.

And the 8th nerve? No vertigo, but she had noted her hearing had been declining of late. I presume aminoglycoside toxicity.

Last year I noted a case of (reversible) renal failure from tobramycin in bone cement.

As a reminder: drugs do not stay where you put them and may concentrate where you do not want them.

Rationalization

Arch Surg. 1976 Jul;111(7):822–5. Neomycin toxicity revisited.

http://www.ncbi.nlm.nih.gov/pubmed/938230

Can J Surg. 1979 May;22(3):274–7. Nephrotoxicity and ototoxicity following irrigation of wounds with neomycin.

http://www.ncbi.nlm.nih.gov/pubmed/436029

Ann Thorac Surg. 1996 Feb;61(2):772. Aminoglycoside toxicity after sternal wound irrigations.

http://www.ncbi.nlm.nih.gov/pubmed/8572818

Chapter Eighty-Three

Metastatic complications

May 29, 2015

The patient has three days of sustained Staphylococcal bacteremia. That’s endocarditis. It turns out to be MSSA, so after three days of vancomycin, the patient is placed on nafcillin.

He had some curious neurologic symptoms on admission. Shoulder tingling and thigh numbness, but the muscles and reflexes were normal.

A pan-MRI of the spine showed a C4 herniated disc, but no epidural abscess. The disc was a wee bit more inflamed than I would have thought.

Several years ago (I thought I wrote about it on this blog, I guess not) I had a patient I think seeded his preexisting herniated disc with S. aureus. While there is an interesting literature of chronic infections in some herniated discs, there were no PubMed reports at the time of acute seeding of a herniated disc with S. aureus. And it is still the case.

Still, given the new symptoms and the slightly odd appearance of the disc on MRI, I was worried Staph had seeded the disc in this patient. Neurosurgery saw the patient and found no acute indication for surgery, and for the next 48 hours, he remained neurologically unchanged.

Because it was the C-spine, we had arranged for a follow-up MRI. An hour before the scheduled MRI, the patient became acutely hemiparetic. The MRI showed maybe some increase in cervical epidural inflammation and off to the OR.

The surgeon was surprised at the lack of pus in the epidural space, although the disc was more mushy than usual, and the gram stain showed gram-positive cocci in clusters. It looks like the S. aureus did seed the disc.

Post-op? He was a T5 deficit, straight across, like a transverse myelitis. Why is that? The neuro deficits are multiple levels away from the pathology on the MRI, and what was found at surgery does not account for the findings.

S. aureus is also called coagulase positive Staphylococcus for a reason. It really likes to cause clot, and given the abrupt onset of the symptoms and location, I suspect this is a vascular event rather compression from the epidural abscess since we never found a compressive epidural abscess.

It happens.

Bacterial myelitis may occur in isolation, and the diagnosis should not be discounted when evaluation shows an absence of a contiguous or systemic source of infection.

I suspect the MSSA led to thrombosis of the spinal arteries and transverse myelitis. It could have been embolic, although the ECHO was negative for vegetations, and there were no other embolic events.

Embolic spinal cord infarction is even more unusual. I find no cases associated with endocarditis, just patent foramen ovale.

Repeat MRI in a few days may give further information.

That is one of the problems with infections. Even when you do everything right, something unexpected will sometimes rear up and bite you.

Rationalization

Spinal Cord. 2014 Aug;52 Suppl 2:S1–2. doi: 10.1038/sc.2014.69. Transverse myelitis due to Staphylococcus aureus may occur without contiguous spread.

http://www.ncbi.nlm.nih.gov/pubmed/25082374

MR of Staphylococcal Myelitis of the Cervical Spinal Cord.

http://www.ajnr.org/content/18/3/455.full.pdf

Spinal cord embolism.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC496222/?page=1

Spinal Cord Infarction and Patent Foramen Ovale: Is There a Link?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105946/

Chapter Eighty-Four

Cheap and Easy

Jun 3, 2015

The patient has endocarditis with lots of emboli: CNS on MRI and legs by exam. Curiously, none in the eyes. Usually, when they have CNS emboli, you see them in the conjunctiva. His creatinine is markedly elevated, I presumed from emboli as well, although there was no hematuria. We did not go looking because he didn’t need the dye load.

Until today. His fevers resolved over a week as did his leukocytosis, but then both returned around day 10. He also remained hemolytic: high LDH, low platelets, and haptoglobin, schistocytes on the smear. I figured it was due to the valves, both the aortic and mitral are involved.

But with the new fevers, we needed to looking for pus to drain. So we did, as is the slang of the day, a pan-scan. I had one resident who calls a CT the answer donut, which I kind of like. So often we get an answer from the CT. Like this time:

An aneurysm in the rectus abdominous muscles, off the distal inferior epigastric artery, that has been bleeding into the abdominal wall.

There was nothing there on a CT from several months ago, so most likely mycotic in origin and explains the fevers and hemolysis.

I did not even remember there was a distal inferior epigastric artery, I had to look it up.

There are a few pseudo-aneurysms in this artery reported, some from trochars after laparoscopic and other surgeries and one from a peritoneal tap, but none with endocarditis.

A literature review revealed another 15 cases. Most cases were iatrogenic (13/16) complicating abdominal wall procedures. Treatment options included open surgery (8 cases), percutaneous coil embolization (6), ultrasound guided thrombin injection or ultrasound guided compression (2). The selected treatment (surgical or non-surgical) was not affected by the size of the aneurysm (p=0.6) and was successful in all patients. However two of the non-surgically removed lesions (25%) remained unchanged in size for a long time causing discomfort. IEA false aneurysms represent an uncommon entity. Open surgery for IEA false aneurysms is easy and cheap.

Cheap and easy. Not adjectives I usually apply to surgery.

I see a lot of endocarditis, but not a lot of mycotic aneurysms, perhaps because I don’t go looking. In 81 consecutive patients

Brain CT/CTA revealed that 51 patients had evidence of cerebral embolization, of them, 17 were clinically silent. Twenty-six patients (32%) had ICMA (intracranial mycotic aneurysms), of whom 15 were clinically silent. Among the patients with ICMAs, 11 underwent endovascular treatment and 2 underwent neurovascular surgery.

Givens one pause. But suggests most get better with no specific therapy and one should worry only if they are heading for anticoagulation.

A coil into an MRSA filled artery just doesn’t sound like a good idea. So now the ball is in the surgeon's court for the cheap and easy solution.

Rationalization

Eur J Vasc Endovasc Surg. 2007 Feb;33(2):182–6. Epub 2006 Oct 20. Inferior epigastric artery false aneurysms: review of the literature and case report.

http://www.ncbi.nlm.nih.gov/pubmed/17055755

PLoS One. 2015 Mar 30;10(3):e0118616. doi: 10.1371/journal.pone.0118616. eCollection 2015. Impact of routine cerebral CT angiography on treatment decisions in infective endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/25823006

POLL RESULTS

Adjectives that I do not apply to medicine

• Cheap 17%
• Easy 4%
• Harmless 54%
• Obvious 4%
• Simple 13%
• Other Answers 9%
  • common
  • magic stuff.
  • normal

Chapter Eighty-Five

Rash Treatments

Jun 5, 2015

Toxic shock? Septic shock? I am not certain at first. The patient certainly is in shock and has a necrotizing Group A streptococcal soft tissue infection.

The rash? Not present on admission, but he is hypotensive and on buckets of pressors. I had a patient who did not manifest their TSS rash until after they were off pressors. I assume he was too clamped down to get red skin. That was the best explanation I had at the time. Maybe the same process is occurring in this patient.

The palms and soles became red 48 hours into the course, but the eyes are not hyperemic, and the tongue does not look like a strawberry. So I am leaning towards septic shock. Also, the creatinine and calcium are normal; the former should be up and the latter down if it is TSS.

Streptococci certainly like to cause a red rash.

The pyrogenic exotoxins appear to be responsible for many of the manifestations of scarlet fever and toxic streptococcal syndrome described in this review. Administration of streptococcal pyrogenic exotoxin A to animals resulted in fever, hypotension, and other symptoms associated with streptococcal toxic shock syndrome.

But this rash is textbook for neither TSS nor Scarlet fever, at least as I have seen them. Probably some variant; patients never seem to read the textbooks.

The other issue was the best antibiotic, as he had a history of a type 1 reaction to penicillin. Sure, clindamycin and IVIG, but there is some resistance to clindamycin, although the resistance rates vary depending on locality. I found reports as low as 2% to the worst case

For GAS blood, skin, and soft tissue isolates taken together, the proportions of clindamycin resistant isolates were significantly higher in 2012 and 2013 (23% and 17%, respectively) compared with the two previous years (3%, p<0,001). data-preserve-html-node="true"

Still, a 1 in 50 chance of clindamycin resistance is, to my mind, too common to bet someone's life on. I have a bias towards greater than 1 in 1000, having seen patients die of resistant organisms when the odds were longer than 2% that the initial choice would be wrong. I like a belt and suspenders when I am treating empirically.

They opted for linezolid in the middle of the night, and I can’t say I would gainsay their choice. It does mess with toxin production, and there is no reason to suspect it would not be effective.

In the end, the patient did fine, and I suspect it had little to do with the antibiotics. The infection was debrided, and, as we all know, nothing heals like cold steel in the hands of a good surgeon.

Rationalization

Clin Microbiol Rev. 2000 Jul; 13(3): 470–511. PMCID: PMC88944 Pathogenesis of Group A Streptococcal Infections.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88944/

Clin Microbiol Rev. 2013 Jul; 26(3): 422–447. doi: 10.1128/CMR.00104–12 PMCID: PMC3719495 Staphylococcal and Streptococcal Superantigen Exotoxins

\https://www.ncbi.nlm.nih.gov/pubmed/23824366

Acta Derm Venereol. 2002;82(6):449–52. Two men with toxic shock syndrome presenting with targetoid and spotty skin rashes.

https://www.ncbi.nlm.nih.gov/pubmed/12575853

I do love these old papers: Br Med J. 1870 Dec 24; 2(521): 676–677. PMCID: PMC2261562 On Scarlet-Fever, with Special Reference to Pathology and Treatment.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2261562/

Eurosurveillance, Volume 20, Issue 18, 07 May 2015 Research articles CLINDAMYCIN RESISTANT EMM33 STREPTOCOCCUS PYOGENES EMERGED AMONG INVASIVE INFECTIONS IN HELSINKI METROPOLITAN AREA, FINLAND, 2012 TO 2013

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21117

Curr Ther Res Clin Exp. 2012 Jun;73(3):86–102. doi: 10.1016/j.curtheres.2012.04.002. Linezolid effects on bacterial toxin production and host immune response: review of the evidence.

http://www.ncbi.nlm.nih.gov/pubmed/24648596

Kansenshogaku Zasshi. 2004 May;78(5):446–50. A case of invasive group A Streptococcus infection which was successfully treated with linezolid.

https://www.ncbi.nlm.nih.gov/pubmed/15211868

POLL RESULTS

I feel comfortable betting my patient’s life and giving antibiotics when resistance is likely.

• 1% 11%
• 0.1% 6%
• What? Bacteria can be resistant to vancomycin and Zosin? 6%
• I give powerful, big gun, strong antibiotics so do not worry. 21%
• never, but at some point you have to treat and hope. 49%
• Other Answers 6%
  • futile
  • depends on the alternatives, and on the reason for not using the first choice.

Chapter Eighty-Six

Medical Spalt

Jun 10, 2015

I am often asked to weigh in on whether a culture is real or not. ‘Real’ is medical shorthand for clinically relevant or a contaminant since the cultures are real. I don’t deal in the imaginary here.

The patient is an elderly male with long-standing inflammatory arthritis on low dose prednisone and weekly methotrexate.

He has his wrist operated on six months ago, and the pathology was consistent with his underling disease, not an infection.

But the wrist did not get better. Increasing redness and swelling, he had another I&D. This time cultures were sent, and it grew a mold.

OK. A mold. Given the host, I would expect Aspergillus.

But no.

Arthrographis kalrae

Ever heard of it? Me neither.

It is a soil organism found in compost and decaying plants, and the patient's hobby is gardening, so I have a good exposure, a susceptible host, and a compatible exam. There is rubor, dolor, calor tumor along the radial side of his wrist, but the joint moves without the marked pain I would anticipate with an infected joint.

It is hard out there for a mold. Arthrographis

produce only poorly differentiated arthroconidial asexual morphs in culture.

Sounds like a Portland bar.

But the Pubmeds reveal only 16 hits and one each for a hodgepodge of infections.

Real? Maybe. Treat? I can’t see how I cannot. Fortunately, Arthrographis is best treated with azoles. So I am left with the always unsatisfactory treat and see if they get better. He did.

And how often do you find a Fungus of the Month in Fine Wood Working? You can Spalt Your Own Lumber with Arthrographis cuboidea. Spalt just sounds wrong, the past tense of some questionable Teutonic practice.

Arthrographis cuboidea is responsible for most of the cotton candy pink stains you see in lumber of hardwoods.

Although A. cuboidea is not a human pathogen, it can turn your workshop pink.

Rationalization

Mycoses. 2014 Apr;57(4):247–8. doi: 10.1111/myc.12151. Epub 2013 Oct 22. In vitro antifungal susceptibility of clinical isolates of Arthrographis kalrae, a poorly known opportunistic fungus.

http://www.ncbi.nlm.nih.gov/pubmed/24147779

Persoonia. 2014 Jun;32:102–14. doi: 10.3767/003158514X680207. Epub 2014 Mar 10. Phylogenetic circumscription of Arthrographis (Eremomycetaceae, Dothideomycetes).

http://www.ncbi.nlm.nih.gov/pubmed/25264385

Spalt Your Own Lumber: Fungus of the Month – Arthrographis cuboidea

https://www.finewoodworking.com/2010/05/01/spalt-your-own-lumber-fungus-of-the-month-arthrographis-cuboideaixzz3cikv16FK

Chapter Eighty-Seven

Pull or Wire

Jun 15, 2015

S. aureus bacteremia is a common enough cause of consultation. Even though it is common, there are little wrinkles in each case.

This wrinkle is a dialysis patient. There is MSSA in the blood, but the two positive cultures are from the arms. No cultures were obtained from the catheter, and then he was started on antibiotics.

Does the catheter need to be pulled?

Yep.

It is probably involved, although I need to check and see if cultures are positive as well.

The guidelines are clear: pull the catheter if it is infected with S. aureus. One, the catheter probably can’t be salvaged. And two, if they do fail therapy and get bacteremic again, they have the same high risk of a metastatic complication, at maybe 20–30%, depending on co-morbidities.

The higher rates of IE were observed in injecting drug users (IE: 38%) and patients with prosthetic (IE: 33%) or native valve disease (IE: 20%), but 40% of IE occurred in patients without heart disease nor injecting drug use.

So why take the risk of salvaging the line? Usually, because those whose job it is to place the catheter don’t like to take them out and often the patient has limited access options.

So rather than take the catheter out, how about an exchange over a wire? Not a bad option, even for S. aureus infections.

There was no difference in tunneled dialysis catheter survival between study and control groups (P = 0.46). Median survival time was 96 days for study catheters and 51 days for controls; survival curves were closely superimposed. There also was no difference among the three staphylococcal groups in terms of catheter survival (P = 0.31). The median time until catheter removal was 143 days for SE, 67 days for CNS, and 88 days for SA-infected catheters.

Now here is my brilliant idea, and I think all my ideas are brilliant. The issue when changing a catheter over a wire is the old catheter can infect the wire, which in turn infects the new catheter.

What someone needs to do is a trial alcohol locking both catheters during the exchange. Even S. aureus can’t survive that 60% alcohol and the brief exposure should have no adverse effects on the dialysis catheter.

Great idea, huh? And there is nothing on PubMed.

Now someone needs to make my idea a reality.

Rationalization

PLoS One. 2015 May 28;10(5):e0127385. doi: 10.1371/journal.pone.0127385. eCollection 2015. Staphylococcus aureus Bloodstream Infection and Endocarditis  A Prospective Cohort Study.

http://www.ncbi.nlm.nih.gov/pubmed/26020939

Cardiovasc Intervent Radiol. 2011 Dec;34(6):1230–5. doi: 10.1007/s00270–011–0180–4. Epub 2011 May 13. Staphylococcus-infected tunneled dialysis catheters: is over-the-wire exchange an appropriate management option?

http://www.ncbi.nlm.nih.gov/pubmed/21567272

Kidney Int. 2000 May;57(5):2151–5. Bacteremia associated with tunneled dialysis catheters: comparison of two treatment strategies.

http://www.ncbi.nlm.nih.gov/pubmed/10792637

Chapter Eighty-Eight

It is Natural, Therefore Harmless

Jun 17, 2015

The patient is a female with well-controlled HIV, CD4 in the normal range although she has not been on her meds recently.

She has a boil on her face that she squeezes and over the next several says it spreads, red and blistering with a slightly raised border. She is admitted with facial cellulitis.

She has no fevers or chills and the WBC is normal. Placed on vancomycin, it does not improve.

When is cellulitis not cellulitis? A lot of the time. If it is not cellulitis, then what is it? Well,

do an initial diagnostic work-up directed by the findings from a detailed history and complete physical examination.

Detailed history. It’s what I do. But I do an informed detailed history, and one of my favorite cellulitis mimics is contact dermatitis.

Patients put all sorts of ointments and salves on their skin and will never, ever tell you unless you ask direct questions. Tea tree oil, aloe vera, lavender and triple antibiotic ointment have been prior causes of contact dermatitis in my patients. So I ask.

She sees a Not a Doctor (ND) who keeps her supplied with a variety of nostrums including a salve that contains

Comfrey, Calendula, Oregon Grape Root, Lavender, Essential Oil Blend, Olive Oil, Beeswax.

With the directions: Apply liberally and often to affected area.

Liberally and often. A great way to make a contact dermatitis accelerate.

In this case it was probably the Calendula, from the marigold plant, part of the Compositae family, or the lavender. Or both.

We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.

The other two botanicals have no case reports on the PubMeds.

HIV patients tend to have more drug reactions. Are they prone to contact dermatitis? Perhaps. But there is not a lot I could find.

Doing nothing should accelerate her healing. It did.

Rationalization

Naturopathic Diaries: Confessions of a former naturopath.

http://www.naturopathicdiaries.com/. A must read.

Science-Based Medicine: Guide to Naturopathy (Science-Based Medicine Anthology Book 3) Kindle Edition by Mark Crislip (Editor), Steven Novella (Editor), David Gorski (Editor)

Ann Intern Med. 2005 Jan 4;142(1):47–55. Narrative review: diseases that masquerade as infectious cellulitis.

http://www.ncbi.nlm.nih.gov/pubmed/15630108

Contact Dermatitis. 2001 Nov;45(5):269–72. The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.). http://www.ncbi.nlm.nih.gov/pubmed/11722485

Contact Dermatitis. 1999 Aug;41(2):111. Facial ‘pillow’ dermatitis due to lavender oil allergy.

http://www.ncbi.nlm.nih.gov/pubmed/10445700

J Am Acad Dermatol. 1999 May;40(5 Pt 1):777–9. Contact dermatitis in subjects infected with HIV type 1.

http://www.ncbi.nlm.nih.gov/pubmed/10321613

Chapter Eighty-Nine

No Other Explanation

Jun 19, 2015

The patient is an elderly female who has not felt well for at least a month. Nothing specific, just a general failure to thrive. Then she developed 48 hours of fevers and chills and was admitted.

Blood cultures grow 4 of 4 gram-positive cocci and 1 of 4 a small gram-negative rod. So they call me.

NIDDM and, she says, acute rheumatic fever as a child, are her only prior problems.

The exam has a pair of loud murmurs over the aortic and mitral valves, and some rotten teeth stumps that she has not been able to afford to get repaired.

I expect a viridans strep and perhaps a HACEK. And I would be wrong.

Abiotrophia defectiva. Sounds like a zombie anime. And Pasteurella canis. Both were called by the MALDI-TOV.

TEE: lots of valvular pathology but no distinct vegetation.

So the Abiotrophia is likely endocarditis. No other reason for that in her blood.

The Pasteurella? No cases of P. canis endocarditis in the literature and the number of cases of infections from this organism would define ‘smattering.’ She has a dog but no sea lions.

Four strains from California sea lions (Zalophus californianus) made up group I, which was classified with Pasteurella canis.

She has no good exposure like a bite or licking. So I am not so sure it is on a valve, but I cannot find another reason for the bacteremia.

I have had a few cases of Abiotrophia that were remarkably lacking in symptoms. I had an IVDA I treated, I thought successfully, who was lost to follow up due to the siren call of heroin who returned a year later with the same Abiotrophia in her blood. I can’t really believe it was relapse OR reinfection given the time lag and the rarity of the organism.

I wonder if Abiotrophia accounted for the failure to thrive, and it was the secondary Pasteurella infection that led to the fevers and chills.

She is allergic to PCN (throat closed), so it’s ceftriaxone and gentamicin for now.

Rationalization

Scand J Infect Dis. 2011 Mar;43(3):234–7. doi: 10.3109/00365548.2010.535559. Epub 2010 Nov 22. Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis: a case report of a patient with mitral valve infective endocarditis caused by Abiotrophia defectiva.

http://www.ncbi.nlm.nih.gov/pubmed/21091125

J Vet Med Sci. 2012 Aug;74(8):1091–4. Epub 2012 Apr 20. The in vitro activity of 15 antimicrobial agents against bacterial isolates from dogs.

http://www.ncbi.nlm.nih.gov/pubmed/22516694

J Zoo Wildl Med. 2012 Dec;43(4):828–35. Occurrence of Pasteurellaceae bacteria in the oral cavity of selected marine mammal species.

http://www.ncbi.nlm.nih.gov/pubmed/23272350

J Heart Valve Dis. 2012 Mar;21(2):260–2. Pasteurella multocida endocarditis.

http://www.ncbi.nlm.nih.gov/pubmed/22645864

Chapter Ninety

Is It Real?

Jun 22, 2015

The Buddha may have said that life is an illusion but germs? They are real. Beauchamp was so wrong. I am often asked if a particular organism is real. It is always real. The question is whether the bug is clinically important.

The patient is a female with a resected lung cancer. Post-op she has a pneumonia and develops a large effusion.

The effusion is tapped, recurs, and a chest tube is placed, and she develops an air leak.

One thing leads to another, and a mold grows from both a bronchoscopy sample and the pleural space. The galactomannan is negative on the BAL, and the 1-3-beta-D-glucan is negative in the blood.

They call me.

Is the mold real?

Yep. That's a real mold you betcha.

I call the lab. What does it look like?

Scedosporium they reply, but which one will take time.

Scedosporium is real and probably clinically important. Finding a mold in the bronchoscopy and pleural space suggests that there is/was a bronchopleural fistula and may account for the air leak.

There is a great Scedosporium review (see below) but when I read a sentence like

The agent of pseudallescheriasis is Pseudallescheria boydii (formerly Petriellidium boydii and Allescheria boydii). The anamorph (asexual state) of Pseudallescheria boydii is Scedosporium apiospermum (formerly Monosporium apiospermum). Some reports of pseudallescheriasis have attributed the disease to S. apiospermum, the anamorph name. Many isolates of Pseudallescheria boydii do not form cleistothecia, the characteristic sexual structures&

my focus wanders.

I want to know three things.

How best to kill it. Voriconazole.

Does it make 1-3-beta-D glucan? Yes. So a negative blood test suggests it has not spread beyond the lung.

And is the patient immune-compromised enough? Not really. She has had no chemo or radiation, and she is otherwise without medical problems. Resected lung cancer just doesn't seem like enough disease risk from what I can find on the PubMeds. Maybe it was colonizing the airway and took advantage of the surgery to slip into the pleural space. Colonization does occur occasionally, so maybe.

But the odds are it is a pathogen

Cultures positive for Scedosporium spp. had a higher PPV (9.1 100%) than did cultures positive for non-Scedosporium spp. (2.8- 69.4%)

and, as is often the case in ID, I can't prove it isn't a pathogen.

So we put her on voriconazole, and she slowly gets better. Proof/pudding and all that.

Rationalization

More than you ever wanted to know: Infections Caused by Scedosporium spp.

http://cmr.asm.org/content/21/1/157.full

Cancer. 2004 Jan 1;100(1):165 72. The significance of isolation of saprophytic molds from the lower respiratory tract in patients with cancer.

http://www.ncbi.nlm.nih.gov/pubmed/14692037

Epidemiology of the airway colonization by Scedosporium apiospermum during cystic fibrosis.

http://www.aspergillus.org.uk/content/epidemiology-airway-colonization-scedosporium-apiospermum-during-cystic-fibrosis

Antoine Béchamp

https://en.wikipedia.org/wiki/Antoine\_B%C3%A9champ

POLL RESULTS

Life is

• an illusion 8%
• a box of chocolates 11%
• a cereal 4%
• a treadmill to oblivion. Fred Allen 15%
• better than the alternative 55%
• Other Answers 7%
  • DNA replication
  • not necessarily...
  • Life is all about choices and understanding. Experience and reading go hand in hand.
  • life. Pa paa paa ra ra.
  • an electrochemical gradient

Chapter Ninety-One

Siren Call

Jul 1, 2015

I just returned from a trip to Chicago, where I gave a few talks at the SMACC conference. Nothing like being the last speaker on the last day, watching the room slowly empty, I hope because they had a plane to catch and not that they knew I was coming up on the list of speakers. Well, someday the talks will be on-line, and you will be able to hear what so many missed live.

I think Chicago is the best city I have visited in the US to date. Much better than New York, where I was a month ago. But I had forgotten the concept of humidity; 70 in Chicago seems much hotter than 90 in the Great Pacific NW. And deep dish pizza is a great way to rapidly add extra pounds.

Time off the wards means no cases for the blog, and the heatwave here the Great Pacific NW means fewer infections.

Before I left for humid, er, Second City, I saw a heroin user with S. aureus bacteremia who had been admitted the night before.

On admit, there had been nothing striking on the exam. Now? She was mostly agitated, asking for pain medications, but her gestures were striking. She was moving her arms like a C-spine injury.

I asked her if she was weak or numb, and she did mention both her hands were numb.

But on exam? No grip, no movement of her legs. And she had not noticed. I cut the H&P short and ordered a stat MRI looking for the epidural that should be there.

Epidural abscesses always scare me as they are so easy to miss and progress so fast. I have another patient with MSSA bacteremia/endocarditis who is paralyzed on a vent. I fret that when we could be missing an epidural, since it is pain or weakness that leads to an evaluation, and a paralyzed ventilated patient will not mention either. We can still follow along with a train of four, but it is unsatisfactory. A couple of times, we have awaked these patients, and they had a complete flaccid paralysis. They had ICU myopathy, not an epidural abscess, but it sure scared the hell out of me. As I say, I hate epidural abscesses.

We call the neurosurgeon, ordered the MRI, and I left to catch a plane after sign-outs.

When I get back? Big cervical epidural abscess drained by the neurosurgeon. The patient? As soon as she could walk, she left AMA. I could not believe it. I have seen a lot of addicts in my career who could not resist the siren call of heroin, but never a patient who was almost a quad from an epidural. It will not end well.

I am always amazed at the power addictions have over people, and not just drugs.

Rationalization

Peripheral Nerve Stimulator - Train of Four Monitoring.

http://emedicine.medscape.com/article/2009530-overview

Siren

https://en.wikipedia.org/wiki/Siren\_(mythology)

POLL RESULTS

Portland is the best city to live in. The best US city to visit is

• Chicago 15%
• New York 20%
• Boston 6%
• San Franciso 19%
• New Orleans 22%
• Other Answers 19%
  • Phoenix
  • Seattle
  • Buffalo
  • Pittsburgh
  • Philadelphia,\The City of Falling-Down-Drunk.\
  • Pittsburgh
  • Budapest; especially Óbuda
  • Washington, DC

Chapter Ninety-Two

Back. In Black

Jul 13, 2015

Back from Sunriver. Vacation is over. Sigh. While I really do have the best job* on the planet, hiking, biking, golfing, eating, and drinking beer in Eastern Oregon is so much better. Oh well, I am only six PowerBall numbers away from retiring.

Every day away from work generates two days of paperwork, and I have to pick up a whole new service. It is always easier to take care of patients from scratch than to pick up their care mid-stream. Unless you are a urologist. But I should quit whinging.

The patient has a permanent central line for the last three years and comes in with fevers and lethargy. She has numerous medical problems, the only relevant one being IDDM.

The blood grows a yeast in three sets of cultures, and the line is pulled. The tip has heavy growth yeast as well. But which one?

You would anticipate Candida, but the lab thinks maybe a non-neoformans Cryptococcus, but it is sent off for identification.

Exophiala dermatitidis.

Never heard of it. Well, I guess I heard of it once, since there is an entry in my app that now needs some serious updating. It is depressing how much I have read and written in the last 30 years but do not remember. How did people practice in the era before the peripheral brain that is the interwebs?

Exophiala dermatitidis. Why try and be original when I can cut and paste?

Exophiala dermatitidis (Wangiella dermatitidis) belongs to the group of the so-called black yeasts. Thanks in part to its thick and strongly melanized cell walls, E. dermatitidis is extremely tolerant to various kinds of stress, including extreme pH, temperature and desiccation. E. dermatitidis is also the agent responsible for various severe illnesses in humans, such as pneumonia and keratitis, and might lead to fatal brain infections…

This is not the black mold found in the chemtrails sprayed by black helicopters flown by men in black. Nope. That is Stachybotrys. This is a black yeast. Different.

And why do yeasts and mold make melanin in the first place? It is not like it has to worry about sunburn living sewage pipes. It turns out that

Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs

and

Melanin has been referred to as ‘fungal armor’ due to the ability of the polymer to protect microorganisms against a broad range of toxic insults.

To continue with more interesting cuts and paste. Cut and pastes. Cuts and pastes.

E. dermatitidis is of special medical importance since it causes a variety of severe illnesses in humans: it is a causative agent of keratitis, of subcutaneous phaeohyphomycosis, and of chromoblastomycosis, and may cause pneumonia. Further, the fungus is neurotropic and causes fatal brain infections, and it plays an important role in patients with cystic fibrosis…

However, species of Exophiala show high prevalence in the human environment and seem to be rather frequent in sauna and steam bath facilities, in sink drains, and in drinking water. Examinations of bathwater and sludge in drainpipes that are warmed daily to over 42°C have identified several species of this medically important genus. Recently, mass growth of dark fungal biofilms on water taps and associated habitats was observed in various German drinking water distribution systems…

Interestingly, besides the human related habitats which are characterized by rather high temperatures, strains of E. dermatitidis have been isolated from glaciers—e.g. the Calderone glacier in the Apennines —as well as in the Arctic and Antarctic environments. Furthermore, Gunde-Cimerman (personal communication) is suggesting that natural spring water is a possible source of the fungi and is the vehicle by which it enters the human environment…

I can find nothing by history for a specific exposure that led to the catheter infection, and given its ubiquity, all that is probably needed is a touch of bad luck and opportunity.

There are a smattering of line infections with this organism on the Pubmeds, mostly in patients with compromised immune systems. The treatment has depended more on medication availability, with amphotericin popular in the pre-azole era. As azoles came online, they have also been used. At least by MIC’s the choices are

…posaconazole, 0.125 μg/ml; itraconazole, 0.25 μg/ml; voriconazole, 0.5 μg/ml; amphotericin B, 0.5 μg/ml; isavuconazole, 1 μ/ml; caspofungin, 8 μg/ml; anidulafungin, 8 μg/ml and fluconazole, 16 μg/ml…

Given the cost, I think I will go with itraconazole, and there is some success with the medication. I suspect that pulling the line is mostly curative, but yeasts in the blood make me nervous not to treat.

Rationalization

PLoS One. 2015 Jun 10;10(6):e0127103. doi: 10.1371/journal.pone.0127103. eCollection 2015. From Glacier to Sauna: RNA-Seq of the Human Pathogen Black Fungus Exophiala dermatitidis under Varying Temperature Conditions Exhibits Common and Novel Fungal Response.

http://www.ncbi.nlm.nih.gov/pubmed/26061625

Med Mycol. 2011 Nov;49(8):819–24. doi: 10.3109/13693786.2011.583285. Epub 2011 May 26. Microdilution in vitro antifungal susceptibility of Exophiala dermatitidis, a systemic opportunist.

http://www.ncbi.nlm.nih.gov/pubmed/21612562

Curr Opin Infect Dis. 2003 Apr;16(2):91–6. Melanin and fungi.

http://www.ncbi.nlm.nih.gov/pubmed/12734441

Mycopathologia. 2008 Apr-May;165(4–5):331–9. Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview.

http://www.ncbi.nlm.nih.gov/pubmed/18777637

* my grandmother always said, with a thick Massachusetts accent, 'a job is what a dog does on the carpet.'

Chapter Ninety-Three

Tolerance

Jul 17, 2015

What a week. I had five consults a day this week, plus the usual meetings and clinic and teaching and life. I have not been this continuously busy in a while. At least a half-dozen curiosities to write about in the days to come, but the striking thing is I just do not have the stamina I once did. Being 58 sucks, and I am a healthy 58. End of the workday and I am, as my Nana used to say, too pooped to pop. Hmm. Interesting now that I look up the origin of the phrase.

I had a patient with a superficial wound infection and MSSA bacteremia. Work up, including a TTE, was negative for metastatic infection, her fevers went away immediately, and repeat blood cultures were negative.

I gave him two weeks of nafcillin. Within a day of stopping therapy, he was febrile, and blood again grew MSSA. Again, workup was negative, including a TTE. He has no comorbidities or murmurs, and since I was going to treat for six weeks for endocarditis no matter what the TEE, I didn’t order one. Clinically he responded immediately to the antibiotics.

At six weeks, the antibiotics were stopped, and within 48 hours, he was febrile, and again the BC grew MSSA. Expletive deleted.

This time I ordered the TEE, and there is a vegetation. OK. I proved what I already knew he had. The question is why he failed.

Yeah, I know that no therapy is 100%, but I cannot remember a failure of nafcillin for endocarditis, where the patient did perfectly for the entire course. Most of my endocarditis failures are poor hosts, poor compliance, prosthetic valves, or do poorly from the beginning.

Back in the day, we fretted about tolerant S. aureus: organisms whose MBC was much greater than the MIC.

The idea has become passe probably as

In vitro, bactericidal test results were not valid predictors of clinical outcome.

and

In addition, patients infected with tolerant organisms remained febrile longer than those infected with nontolerant strains but did not require additional antibiotics for cure.

So is tolerance the reason? That’s my story, and I am sticking with it.

I find no pus to drain elsewhere, no ring abscess, and he is hesitant to have a valve replacement. Given that every other anti-staphylococcal antibiotic is worse than nafcillin, this time I am going to treat like prosthetic valve endocarditis, adding rifampin and a short course of gentamicin.

Wish me luck.

Postscript

It worked.

Rationalization

J Pediatr Orthop. 1996 Jul-Aug;16(4):518–21. Microbiological tolerance in orthopaedic infections: delayed response of septic arthritis and osteomyelitis of the hip due to infection with tolerant Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/8784710

Am J Med. 1986 Jul;81(1):43–52. Relationship of staphylococcal tolerance, teichoic acid antibody, and serum bactericidal activity to therapeutic outcome in Staphylococcus aureus bacteremia.

http://www.ncbi.nlm.nih.gov/pubmed/3524225

Ann Clin Microbiol Antimicrob. 2011 Jun 9;10:26. doi: 10.1186/1476–0711–10–26. Bactericidal activity of oxacillin and glycopeptides against Staphylococcus aureus in patients with endocarditis: looking for a relationship between tolerance and outcome.

http://www.ncbi.nlm.nih.gov/pubmed/21658248

Antimicrob Agents Chemother. 2008 Jul;52(7):2463–7. doi: 10.1128/AAC.00300–08. Epub 2008 May 12. Addition of rifampin to standard therapy for treatment of native valve infective endocarditis caused by Staphylococcus aureus.

http://www.ncbi.nlm.nih.gov/pubmed/18474578

POLL RESULTS

As I age, I have more issues with

• stamina 4%
• stamina (wink wink nudge nudge) 2%
• memory 8%
• word finding 22%
• giving a rats ass 61%
• Other Answers 4%
  • I know it, but I forget what it's called.....
  • hypocrisy.

Chapter Ninety-Four

Primary Progression?

Jul 20, 2015

Still crazy busy. And the weekend was crazy busy, with Harefest and my first attempt at deep dish Chicago pizza (baked in the smoker/grill, not to brag, but unbelievably delicious). Oh well, I guess I can rest in my grave.

The patient has floaters in one eye. She sees her ophthalmologist who sees some sort of funky retinitis.

The ophthalmologist suspects TB, among other things, and places a PPD and gets a CT of the chest.

The PPD is whopping positive, and the CT shows bilateral upper lobe scars, cavities, and infiltrates.

They call me, and I suggest that since the patient is homeless, an admission would be the most expeditious way to work her up.

Interesting history. She has never left Oregon, and while she did have a TB exposure 15 years ago, her last PPD, about two years ago, was negative. There is a helpful program in Portland where to gain admission to a homeless shelter, you have to have a documented negative PPD. It has probably helped kept TB rates low in the underprivileged.

Of the three sputa, only one is smear-positive, and that one plus. And the patient has minimal lung symptoms and no consumption.

When you get exposed to TB, you inhale it into the (usually) right lower lobe where it multiplies and spreads hematogenously to the upper lobes, among other areas. Given the paucity of symptoms and AFB on the smear, I wonder if we have caught the TB at the stage of primary extension to the upper lobes, and she is probably controlling the infection on her own. If she had not had eye symptoms, maybe a year from now, all we would see is some apical scarring. So I think we may be seeing the evolution of the primary exposure and not reactivation.

And the retinitis? It happens. But not often. Much of the modern literature concerns IRIS in HIV patients. There are some curious reports from early last century, but then I always enjoy the old literature. Besides actually having antibiotics, the big change in the disease in the last 100 years is using PCR on ocular fluid to make the diagnosis.

Ocular TB usually has a good outcome, and, for fun, I checked a Vitamin D level. Surprisingly normal for an Oregonian.

Rationalization

Clin Exp Optom. 2013 Jul;96(4):428–9. doi: 10.1111/cxo.12008. Epub 2013 Jan 16. Unusual presentation of ocular tuberculosis: multiple chorioretinitis, retinal vasculitis and ischaemic central retinal vein occlusion.

http://www.ncbi.nlm.nih.gov/pubmed/23931632

Int J Infect Dis. 2011 Aug;15(8):e580–1. doi: 10.1016/j.ijid.2010.12.013. Epub 2011 Jun 8. Blurred vision as primary presentation of tuberculosis.

http://www.ncbi.nlm.nih.gov/pubmed/21652253

Trans Am Ophthalmol Soc. 1937; 35: 234–259. PMCID: PMC1315609 The Treatment of Ocular Tuberculosis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315609/?page=1

J Chemother. 2015 Jun;27(3):128–38. doi: 10.1179/1973947815Y.0000000043. Epub 2015 Jun 9. Vitamin D and tuberculosis: a review on a hot topic.

http://www.ncbi.nlm.nih.gov/pubmed/26058744

Chapter Ninety-Five

Uncultured

Jul 22, 2015

The patient is healthy, roughly my age. It is odd the last few weeks that most of my consults have been 58 +/- 2 years old. And mostly healthy except for the disaster that led them to admission. Is the Universe trying to tell me something? I have long noted that I have yet to have a patient on their death bed tell me, “Doc, I wish I had spent more time at work.” I just have two kids to get through higher edumacation; I am in my Nixon mode. Four more years.

Anyway, I wander. The patient comes in trying to die from sepsis, the whole 9 yards of MOSF. Or perhaps the whole 6 feet under. But she survives thanks to modern medicine and the ICU team. They do a complete evaluation looking for a reason and find none. So they call me.

As if I can figure it out. There are a limited number of areas that can become infected, and all the tests have been negative. The only thing left to do is an autopsy, and, as I said, that will not be necessary.

Then the blood cultures pop positive for gram-negative rods. Thin, pointed, and anaerobic.

Ahhh. Cultures. Once I have the name of the organism, and the lab suspects a Fusobacterium, I may have an answer for the why of the sepsis. Although she is a bit too sick for anaerobic infection, especially with no evident source.

But today, after a week of trying, the lab lets me know: Nope. We can’t grow it enough for identification. I am SOL. Sometimes ID is like sitting in a DQ. You can smell the burgers and fried and hear the malts getting made. The stomach growls, and the drool slips down the chin. They call your number, you walk to the counter and get… a glass of ice water. So close, yet so far.

Not being able to culture organisms is par for the course.

Environmental microbiologists estimate that less than 2% of bacteria can be cultured in the laboratory. In the mouth we do rather better, with about 50% of the oral microflora being culturable. For other body sites, the figure is unknown but is likely to be similar to that found in the mouth or higher. For example, the colonic microflora is suspected to be predominantly unculturable.

and

The majority of bacteria will not grow on nutrient medium in the lab. The basic experiment is simple: take a sample from the environment, such as marine sediment or soil, mix with water, vortex, allow it to settle, dilute supernatant and take two droplets. Plate one on a Petri dish with LB medium, and place the other on a microscope slide (adding a dye such as DAPI helps). Count the number of cells under the microscope and the number of colonies on the Petri dish — the result will be “The Great Plate Count Anomaly.” About 100 times more cells will be observed microscopically than colonies counted on the Petri dish. This simple result is one of the most profound puzzles in microbiology, and one of the most significant unsolved questions in biology.

Can’t grow or will not grow; is the problem the lab or the organisms? I do not know as

Many bacteria, including a variety of important human pathogens, are known to respond to various environmental stresses by entry into a novel physiological state, where the cells remain viable, but are no longer culturable on standard laboratory media. On resuscitation from this ‘viable but nonculturable’ (VBNC) state, the cells regain culturability and the renewed ability to cause infection.

For a clinician, it is really annoying, and molecular methods have let us know that there are more things in heaven and earth than are dreamt of in our microbiology. I am looking forward to the day when we can routinely do molecular techniques on blood.

The patient did just fine. I can kill anaerobes. But instead of a full meal deal, I am left with a glass of ice water.

Rationalization

Eur J Clin Microbiol Infect Dis. 2015 May 28. [Epub ahead of print] Are incidence and epidemiology of anaerobic bacteremia really changing?

http://www.ncbi.nlm.nih.gov/pubmed/26017663

Ann Acad Med Singapore. 2015 Jan;44(1):13–8. Anaerobic bacteraemia revisited: species and susceptibilities.

http://www.ncbi.nlm.nih.gov/pubmed/25703492

Unculturable bacteria—the uncharacterized organisms that cause oral infections.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279316/

The Uncultured Bacteria.

http://schaechter.asmblog.org/schaechter/2010/07/the-uncultured-bacteria.html

Clinical detection and characterization of bacterial pathogens in the genomics era.

http://www.ncbi.nlm.nih.gov/pubmed/25593594

Recent findings on the viable but nonculturable state in pathogenic bacteria.

http://www.ncbi.nlm.nih.gov/pubmed/20059548

Chapter Ninety-Six

Five Year Fester

Jul 24, 2015

The history is everything, right? You have to trust the history. But sometimes the story can be kind of odd.

Five years ago, the patient had her gallbladder out. At the time, it was noted on the CT that there was a thick-walled cyst in the liver, maybe an abscess.

Nothing was done about it at the time for reasons I can’t glean from the EMR, and the patient was lost to follow up.

I looked at the old CT. Looked like an abscess to me.

For the next five years, the patient did fine except for some slight, occasional, right upper quadrant, and epigastric pain. But no signs or symptoms of infection. She eventually had a new provider, and a repeat study was done.

Same thick-walled abscess, only it had grown in the interim by about a centimeter. So they tapped it.

Pus and MRSA.

Really? A chronic liver abscess of over five years duration with no symptoms from MRSA? That is what it appears to be. Nothing else grown like Actinomycosis and no risks for other infections or other medical problems.

This is the only infection she has ever had in over 50 years, so some sort of immunodeficiency like CGD seems unlikely.

A ‘cold’ abscess from S. aureus does not surprise me. Everyone once in a while I see a collection of S. aureus with no rubor, dolor, or calor, only tumor, although classically cold abscesses tend to be due to TB or fungi.

But five years? That flabbers my gaster. CT and history suggest it is so, but I can find no bacterial abscess of the liver going on this long. I once had a K. pneumoniae that, by history, festered for about a year before rupturing into the pleural space and then out the chest wall.

Maybe my google-fu is off, but I can’t find anything close to this in duration for S. aureus outside of a Brodie's abscess. But I cannot come up with another explanation.

So an oddity, a record, or I am seeing a pattern that is not there.

Rationalization

Med J Aust. 1956 Oct 13;43(15):567-8. Antibiotic-attenuated chronic staphylococcal abscess simulating early carcinoma in the lactating breast.

http://www.ncbi.nlm.nih.gov/pubmed/13377840

Chapter Ninety-Seven

Do I know what I think I know?

Jul 27, 2015

There is what I know and what I think I know.

I see a lot of diseases. Common diseases for me, such as endocarditis or epidural abscesses, are rare for other physicians. It is what I get for being the only ID doc at three hospitals. All the odd stuff goes through me. And I'm not talking gi tract here.

When I see an unusual bug in what is, for me, a common disease, I tend to say something like “Huh. That is an odd bug to be causing that disease.”

But of course, I have not seen enough cases to really see it all. My vast experience is only in comparison to non-ID doctors. Compared to the experience of the world, I have seen nothing.

As an example, I have seen several cases of endocarditis a month for 30 years, but even with that relatively large experience, I have seen two each of HACEK, completing the pentad twice. I still have yet to see a Q fever or Bartonella endocarditis, and not for a lack of testing.

The patient is on dialysis and has had his catheter in place for over two years. All lines eventually break or get infected, and his became infected with S. epidermidis. Common enough. But he also had back pain, and an MRI showed discitis, osteomyelitis, and an epidural abscess, a tap of which is also growing S. epidermidis.

So I said, “Huh. That is an odd bug to be causing hematogenous discitis.”

I can’t remember ever having seen a coagulase-negative Staphylococcus outside of neurosurgery. But is that indeed the case?

The PubMeds are my electronic eight ball:

Coagulase-negative staphylococci caused infection only in patients who had previous spinal instrumentation.

and a search with ‘hematogenous epidural abscess coagulase negative” results in a “No items found.”

Although S. epidermidis is more common as a cause of pyogenic spondylodiscitis.

Coagulase-negative staphylococci (CoNS) have been reported in 5–16% of cases. Staphylococcus epidermidis is often related to postoperative infections and intracardiac device-related bacteremia.

The patient has never had any spine issues.

So hematogenous spread to the spine and epidural space is as rare as I thought.

So with my one case, I am probably now a world expert on the disease, having seen more than anyone else.

Now for a course of vancomycin.

Rationalization

Medicine (Baltimore). 1992 Nov;71(6):369–85. Bacterial spinal epidural abscess. Review of 43 cases and literature survey.

http://www.ncbi.nlm.nih.gov/pubmed/1359381

Eur Rev Med Pharmacol Sci. 2012 Apr;16 Suppl 2:2–7. Epidemiological and clinical features of pyogenic spondylodiscitis.

http://www.ncbi.nlm.nih.gov/pubmed/22655478

Chapter Ninety-Eight

Does he or doesn’t he? No hairdresser to ask.

Jul 29, 2015

The patient, an otherwise healthy and vigorous middle-aged male, has had several years of intermittent fevers, sweats, and a general failure to thrive.

Work up by his PCP is negative, and he eventually ends up in my office.

Everything is reasonably normal except for the intermittent fevers. Routine labs (while between episodes) are negative.

The only striking thing is he had spent a decade in the rural Philippines with TNTC bug bites and exposures to everything while there; he ate the food, drank the water, swam in fresh and saltwater, etc. But he has been back in the states for about a decade.

So I figured it was between schistosomiasis and malaria, and if malaria, P. malaraie. I had one case of P. malariae in a patient 2 years after leaving the Philippines.

Schistosoma serology was negative, a thick and thin was negative (when ill), but for hoots and giggles, I sent a malaria serology that came back positive.

Hmmm. Important? Or not?

So for further hoots and giggles, I sent off a malaria PCR, and it was negative for all the malarias as well.

So now what?

I was always impressed with Plasmodium malariae Infection in an Asymptomatic 74-Year-Old Greek Woman with Splenomegaly which noted

We report a case of malaria due to P. malariae in a 74-year-old woman from Greece whose illness was reactivated after decades of latency. All manifestations were reversed with a three-day course of chloroquine. Although thick and thin peripheral-blood smears were repeatedly negative, a nucleic acid–based assay detected the infecting species of malaria parasite. Since malaria was eradicated from Greece by about 1950, the patient’s infection most likely lasted more than 40 years, possibly as long as 70.

He had mild splenomegaly on CT. So?

I talked it over with the patient, told him I was not really certain he had malaria, but it may be reasonable to treat. So he received a course of chloroquine and primaquine.

And?

All better. He feels great, the best he as in years, and has no more febrile spells.

But. I always remember the fifth fallacy in infectious diseases, from the classic everyone should read Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy.:

Response implies diagnosis.

As is so often the case, close but not definitive.

Does he or doesn’t he? Got me.

Rationalization

Plasmodium malariae Infection in an Asymptomatic 74-Year-Old Greek Woman with Splenomegaly.

https://www.ncbi.nlm.nih.gov/pubmed/9449730

Br Med J. 1923 Jun 30; 1(3261): 1087–1088. PMCID: PMC2316845 THE TREATMENT OF CHRONIC MALARIA.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2316845/

I love old references.

J Travel Med. 2011 Jul-Aug;18(4):288–91. doi: 10.1111/j.1708–8305.2011.00526.x. Epub 2011 Jun 15. Nephrotic syndrome and unrecognized Plasmodium malariae infection in a US Navy sailor 14 years after departing Nigeria.

http://www.ncbi.nlm.nih.gov/pubmed/21722243

Acta Trop. 1977 Sep;34(3):265–79. Malaria in the Republic of the Philippines. A review.

http://www.ncbi.nlm.nih.gov/pubmed/21558

Am J Med. 1989 Aug;87(2):201-6.

Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy.

https://www.ncbi.nlm.nih.gov/pubmed/2667357

Clairol Does She Or Doesn’t She.

https://www.youtube.com/watch?v=FkxgkquA6sk.

For you youngsters

Chapter Ninety-Nine

-Oma

Jul 31, 2015

The patient has had HIV for decades, having been diagnosed with PJP in the early nineties and meningitis about eight years ago on the east coast. The records of that meningitis are not available, and the patient does not remember the etiology. He has had an undetectable HIV viral load for years, and his CD4 counts hover around 200.

He has had a progressive headache for six months, and he gets an evaluation. CSF and blood are negative for cryptococcal antigen, seronegative for toxoplasma, but the MRI shows an isolated cystic, enhancing something or other in the cerebellum.

So the neurosurgeon takes it out.

Pathology is a cryptococcoma.

Odd. Is this a late sequela from his prior meningitis, festering at the border between cure and progression because of a barely adequate immune system? A new isolated lesion in a barely immunocompetent host? And with the blood and CSF antigen-negative, should he be considered a cure?

Cryptococcoma does occur in immunologically normal people, with perhaps 17 cases in the literature and are maybe more common with C. gattii.

Somehow I thought of cerebral cryptococcomas as an issue with HIV, but there are fewer HIV cases on the PubMeds than there are cases in normal hosts. I suppose it would hard to make a cryptococcoma if you cannot generate an inflammatory response due to HIV.

And it is hard to say for sure without a careful literature review, which is not what I do for a blog post, but there is a suggestion of both negative antigen and a preference for the cerebellum. It has also been reported in cats more than dogs, especially American Cocker Spaniels as well as goats, cows, gorillas koalas, sea lions, and ferrets.

It looks like animals that have their nose in the dirt are particularly prone to Cryptococcus, although the risk or transmission to dogs and cats from companion parrots is overrated. Me? I would never have even considered it,

A number of common misconceptions exist regarding the degree of transmission from companion parrots to dogs and cats&Infections with Mycobacterium spp, Aspergillus spp, Giardia spp, Chlamydophila psittaci, Salmonella spp, Yersinia pseudotuberculosis, Cryptococcus neoformans, Histoplasma capsulatum, Cryptosporidium spp, and avian influenza are often considered possible transmissible diseases, causing pet caregivers unwarranted concerns.

Although I remember a case of Mycobacterium genavense from parakeet transmitted to an AIDS patient. The things I learn writing this blog.

Even though I suspect he was cured with the resection, I opted for an arbitrary course of fluconazole. What the endpoint is going to be is unknown.

Rationalization

Acta Neurochir (Wien). 2010 Jan;152(1):12936. doi: 10.1007/s0070100903118. Epub 2009 Apr 30. Central nervous system cryptococcoma in immunocompetent patients: a short review illustrated by a new case.

http://www.ncbi.nlm.nih.gov/pubmed/19404577

Clin Infect Dis. 2013 Aug;57(4):54351. doi: 10.1093/cid/cit341. Epub 2013 May 22. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii.

http://www.ncbi.nlm.nih.gov/pubmed/23697747

J Am Vet Med Assoc. 2011 Aug 1;239(3):35769. doi: 10.2460/javma.239.3.357. Clinical features and epidemiology of cryptococcosis in cats and dogs in California: 93 cases (19882010).

http://www.ncbi.nlm.nih.gov/pubmed/21801050

AIDS. 1997 Feb;11(2):2556. Identification of Mycobacterium genavense in intestinal tissue from a parakeet using two polymerase chain reaction methods: are pets a reservoir of infection in AIDS patients?

http://www.ncbi.nlm.nih.gov/pubmed/9030378

POLL RESULTS

I worry most about the transmission of pathogens from

• dogs 6%
• mosquitos
• 12%
• birds 0%
• rats 2%
• bipedal humanoids 73%
• Other Answers 6%
  • children
  • toddlers
  • cats

Chapter One Hundred

@idfactoid

Aug 5, 2015

April is the cruelest month. Perhaps. Maybe it is the showers, stirring dull roots with spring rain. I don’t find ole TS’s explanation for the cruelty to be all that compelling.

August is, from an ID perspective, the dullest month. Work is always slow when the weather is good, and everyone, patients and doctors, are on vacation. I had one August where I had exactly one consult the entire month, and that with no insurance. This month is not that bad, two consults so far, both insured, but thin gruel about which to blog.

So instead of a case, some self-aggrandizement. What good is a blog if you can’t pimp yourself?

Every year I do a bored review for the residents where I go through all the pearls and factoids from the MKSAP they need for the boreds. For the most part, it is in one ear, out the other. There is just too much they have to learn there is no human way for them to cram that much information from one session into their brains. As an attending once mentioned, learning medicine is like drinking from a firehose.

I need to hear/read things three or four times before I learn it. I used to give a yearly ID update for grand rounds, and it was always depressing going over the years literature. Every article I had read and talked about on the Puscast, yet I had no memory of reading the majority of them. Sad, really, how hard it is to acquire new information.

So I figure, why not give them a factoid/pearl or three every day? Perhaps with a snide comment to reinforce the learning.

So there is now ID Factoid on Twitter. @idfactoid.

Every day an MKSAP related fact or two, perhaps something cool I learned one of my many Google/Pubmed searches that do not warrant a blog entry, or just an opportunity to regurgitate some bit of ‘wisdom.’

Part of my growing multimedia empire. Because, as I have said so many times before, the world needs more Mark Crislip®.

POLL RESULTS

The world needs

• more Mark Crislip 58%
• much less Mark Crislip. Far less. Please, please, please. 6%
• a chicken in every pot and a good 5 cent cigar 12%
• peace, love and understanding 13%
• kinder gentler Aprils 2%
• Other Answers 10%
  • to relax and chill out.
  • August where the temperature never gets above 35 degrees.
  • less noise
  • A right smart smack on the head.
  • Ross Perot

Chapter One Hundred One

As If I Know

Aug 7, 2015

It turns out that MTW of this week, the link was broken for my beeper on the work intranet. After filling out the form and hitting the submit page, nothing happened. A homeopathic page. What was worrisome after I discovered the problem, many docs said, "Oh, we just figured it out without you." I do not want anyone to think they do not need me. Jeeze.

I occasionally get a consult asking if it is OK to do something to a patient, a procedure, or give a biologic.

The patient has prior MRSA infection, can I put a hip in her? The patient has a positive quantiferon gold and needs infliximab for their psoriatic arthritis, can I give it?

Infliximab. It sounds like forcing the Winter Queen of the Winter Court on a patient.

The patient is a young male with refractory ulcerative colitis for the last year. Steroids have done nothing to stem the tide of the disease, and his course has been complicated by first C. difficile and now CMV colitis.

He can’t eat, has lost 50 pounds, and they want to know from me if it is safe to give infliximab.

As if I know.

CMV colitis is not uncommon in UC; sometimes it acts more like a fellow traveler, other times, it is more symptomatic.

Two pathogens, namely CMV and C. difficile, have been associated with disease exacerbation in specific clinical situations. Whereas C. difficile may produce worsening of the disease in those exposed to broad-spectrum antibiotics, CMV reactivation is seen only in patients with moderate to severe steroid-refractory disease.

I also wonder if CMV causes self-limited GI disease in normal hosts more often than we suspect since we do not look.

In steroid-resistant UC, treating may be of benefit.

Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS.

and

although no randomized controlled trial has been performed to evaluate the efficacy of antiviral therapy in UC patients with CMV infection, some observational studies had showed that CMV infection was associated with steroid-resistant disease and antiviral therapy was beneficial to clinical outcome.

So we added antiviral therapy.

Now they want to add infliximab. Can it be done safely? While there are many cases of CMV with infliximab, I always remember that the plural of anecdote is anecdotes, not data. And the pleural of infection is empyema.

In a series of 73 anecdotes they found

Patients under anti-TNF maintenance therapy are not at higher risk of CMV reactivation in case of flare-up. No reciprocal adverse influence was observed between anti-TNF mabs and CMV infection, suggesting that these drugs must be considered for treating flare-ups associated to CMV reactivation.

So it is probably safe, especially as he is already on antivirals.

I still do not understand why they just do not take the damn thing out. The colon is an overrated organ, it will eventually turn malignant, and having it removed is so much better than UC and its treatments. I speak here from personal experience.

And best of all, when someone tells me I am full of crap, I can say, perhaps, but less than you.

Rationalization

Inflamm Bowel Dis. 2015 Jul 20. Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/26197450

Trop Gastroenterol. 2014 Aug;35 Suppl 1:S12–5. Factors precipitating acute ulcerative colitis.

http://www.ncbi.nlm.nih.gov/pubmed/25735121

World J Gastroenterol. 2015 Feb 7;21(5):1689–90. doi: 10.3748/wjg.v21.i5.1689. Unfavorable outcome of antiviral therapy in cytomegalovirus-positive ulcerative colitis may be due to inappropriate study inclusion in meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/25663793

Inflamm Bowel Dis. 2015 Jul;21(7):1580–6. doi: 10.1097/MIB.0000000000000412. Infliximab Does Not Worsen Outcomes During Flare-ups Associated with Cytomegalovirus Infection in Patients with Ulcerative Colitis.

http://www.ncbi.nlm.nih.gov/pubmed/25933392

Clin Microbiol Infect. 2015 May 21. pii: S1198-743X(15)00531-5. doi: 10.1016/j.cmi.2015.05.016. Symptomatic Cytomegalovirus Gastrointestinal Infection with Positive Quantitative Real Time PCR in Apparently Immunocompetent Patients: a Case Series.

http://www.ncbi.nlm.nih.gov/pubmed/26004014

POLL RESULTS

The last thing I need other doctors to do is

• to think they do not need me 8%
• treat S. aureus bacteremia alone 8%
• call for a stat consult Friday at 4 for a patient that has been in the hospital for a month 42%
• send EBV serologies and then ask me to say what it means 17%
• call an antibiotic strong, powerful or big gun 23%
• Other Answers 2%
  • prep the victim, I mean patient, for a bone marrow aspirate, and repeatedly refer to the local anesthetic as "Nummin' Medicine." Arrrrrgh!!

Chapter One Hundred Two

Swarm

Aug 12, 2015

It has been crazy busy for most of August. Weird. As I have mentioned, the service is historically dead in the water this time of year, and mentally I join it. Who wants to work during August in Oregon?

Sometimes it is the little things that pique my curiosity as I am working up a patient.

It is a middle-age male with a complicated urinary history. They call me because the blood grows Proteus and Enterococcus, but the urine only has a Proteus with a different sensitivity.

That’s fine. I call the lab, they double-check, and the Proteuses (Protei ?) are the same. Happens on occasions.

The Enterococcus? I figure it was in the urine, and the Proteus swarmed over the plate, overwhelming any other organism. Lab confirmed that hypothesis if the Enterococcus was in the urine, there is no way they could tell. Too much swarming Proteus.

Well, there is a way to tell, I suppose if we really needed to bother.

When Proteus mirabilis is suspected, e.g., in cutaneous, digestive, or skin ulcer samples, 2 drops of 90% ethanol solution are added to the cover of the plate. The plate is then incubated upside down as usual for 18 h. The same technique is used to isolate bacteria from mixed primary cultures. This method can be used with all the commercial media routinely used in the laboratory, including blood agar plates. The growth of other bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus group A, B, C, or G, Enterobacteriaceae, and Pseudomonas aeruginosais not impaired.

While I have used the terms swarm and Proteus together all my career, it occurred to me today, why do they swarm? What is the mechanism? I really didn't know. I doubt it is a killer bee invasion.

There are four kinds of swarming, five if you include none: featureless, bull's-eye, dendritic, and vortex. And when they swarm, they really haul. Check out the video link below. A lot more disturbing than killer bees.

Swarming is rare in the bacterial world and only found in three families: Firmicutes, alpha Proteobacteria and gamma Proteobacteria (Proteus).

Swarming is varied, complicated, and has multiple mechanisms. Some bacteria form rafts, others make surfactants, some hyperflagelate (I let you make your own comment), and to judge from the video, some do Busby Berkley synchronized swimming.

For Proteus

scanning electron microscopy of a swarm of Proteus mirabilis revealed extensive rafting and perhaps intercellular bundling of flagella.

Quite the bug. And the name? It was named for the Greek god in the Odyssey, who changed shape to avoid capture.

All cool, of little clinical relevance, and part of what makes ID fun.

Rationalization

J Clin Microbiol. 1999 Oct; 37(10): 3435. PMCID: PMC85602 Abolition of Swarming of Proteus.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC85602/

A field guide to bacterial swarming motility.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135019/

Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis.

http://www.nature.com/nrmicro/journal/v10/n11/full/nrmicro2890.html

Theory of periodic swarming of bacteria: application to Proteus mirabilis.

http://cds.cern.ch/record/449462/files/0007087.pdf

Swarm timelapse

https://www.youtube.com/watch?v=0YYAtPCIMc0

POLL RESULTS

Bacteria should be named after

• Greek gods 22%
• the first patient infected with it 1%
• the discoverer 25%
• me. I want immortality 17%
• funny-sounding nonsense syllables 22%
• Other Answers 12%
  • something humorous and memorable
  • Biological and genomic properties
  • Latin roots "coccus." Makes complete sense.
  • something reasonable, such as special environmental or pathological associations.
  • Characters from science fiction and fantasy. Mr. Jones, you have Jon Snow cerebritis.

Chapter One Hundred Three

Playing it Safe

Aug 14, 2015

The patient is admitted with back pain. He has long-standing osteoporosis from prior steroid use, and CT shows a mid-thoracic compression fracture. Man, those look painful.

Thirty-six hours into the admission, he has a fever. He denies any fevers prior to admission and no constitutional symptoms except he demands a short sleeve short, something about the right to bare arms. Constitutional symptoms. Right to bare arms. Get it? Sigh.

All his blood cultures the next day, 4/4, grow S. lugdunensis. So they call me.

Repeat blood cultures are negative (on antibiotics), but the fevers persist for just short of three days. No vegetation on the valve.

So now what?

The preferred part of the human body for S. lugdunensis is the great toe, so unless the blood culture was drawn by the most unusual technique ever, I can’t see it as a contaminant.

Swabs from the groin and the lower extremities, especially the nail bed of the first toe, often yielded S. lugdunensis but rarely S. aureus. This study shows that S. lugdunensis is an integral part of the normal skin flora, primarily of the lower abdomen and extremities, and that the niches of this coagulase-negative staphylococcus are distinctly different from those of S. aureus. The predominant niches of S. lugdunensis explain why the bacterium is an uncommon contaminant of blood cultures.

In real estate, they say its location, location, location, but S. lugdunensis gets the short end of the location stick

There is only one vertebral body involved, so it is unlikely to be a spine infection. Bacteria always start at the disc space and involve adjacent vertebral bodies. Although I suppose a new compression fracture could be fertile soil for seeding from a bacteremia.

The ECHO is negative, but how long does it take to form a vegetation? I have it in my mind that in the sheep model, it takes a week before a vegetation will show up on ECHO. Is that true? Got me. I learned that fact from an older ID attending as a fellow and have never found a reference, so it is more eminence based than evidence-based medicine

.

And when S. lugdunensis is in the blood, it means endocarditis up to 50% of the time.

So safe, being better than sorry, means a long course of IV antibiotics for maybe endocarditis, maybe back infection. Unsatisfying is it not?

Oh. And S. lugdunensis smells like bleach.

We further observed that S. lugdunensis develops a characteristic odor…this odor has been described as “hypochlorite bleach-like”

But why does it smell like bleach? What is the chemical reason, and what is the purpose of that chemical? Keeping its home clean? The big toe is grotty and could use a good bleaching. But no one has looked that I can find. Bummer. It might be cool.

Rationalization

Clin Microbiol Infect. 2010 Apr;16(4):385–8. doi: 10.1111/j.1469–0691.2009.02813.x. Epub 2009 Jun 6. Staphylococcus lugdunensis in several niches of the normal skin flora.

http://www.ncbi.nlm.nih.gov/pubmed/19519842

N Z Med J. 2012 May 11;125(1354):51–9. Unusually virulent coagulase-negative Staphylococcus lugdunensis is frequently associated with infective endocarditis: a Waikato series of patients.

http://www.ncbi.nlm.nih.gov/pubmed/22595924

J Clin Microbiol. 2011 Apr;49(4):1697–9. doi: 10.1128/JCM.02058–10. Epub 2011 Jan 26. Clinical significance of a single Staphylococcus lugdunensis-positive blood culture.

http://www.ncbi.nlm.nih.gov/pubmed/21270222

Seven alternatives to evidence based medicine.

http://www.bmj.com/content/319/7225/1618

POLL RESULTS

I want micro-organisms to smell

• like bleach 0%
• like butter 5%
• like grapes 12%
• like hay 7%
• like teen spirit. That would be nirvana 67%
• Other Answers 10%
  • not at all
  • Evil Civilizations in Star Trek
  • like a newborn baby's bottom
  • like damp sod.

Chapter One Hundred Four

Save Some Money

Aug 17, 2015

I have seen the patient on and off over the years. He has chronic lymphedema and is occasionally admitted with cellulitis. The last time I saw the patient in the clinic, we had discussed prevention options, but he has well-documented allergies to any of the antibiotics I would consider using for long-term prevention of Group A Streptococcus infections.

I told him that there was no reason to suspect bone infection as he had never had trauma to bone or any chronic soft tissue breakdown like an ulcer to the bone.

He was admitted over the weekend for cellulitis, and the house staff wanted to work him up for osteomyelitis for the recurrent cellulitis. X-rays and more. He refused. Why? Because I had told him that there was no reason to suspect osteomyelitis. Good on him.

And he was right. I saw the patient today, and he is already responding to several broad-spectrum, excessive antibiotics he didn’t need.

He still had not had chronic skin breakdown or bone trauma that could result in a bone infection. So no reason to suspect a bone infection.

Here is a pearl that may save a little money. Osteomyelitis never happens from cellulitis, the diffuse erythroderma with no abscess or ulcer or bone trauma. It is like a reasoned, thoughtful statement from Donald Trump. Yes, in theory in could happen, but in reality? Nope.

And if you go so far as to get a bone scan or MRI? False-positive, and you just wasted some real money.

Save some money and radiation exposure. Osteomyelitis is never, ever the reason for recurrent cellulitis and cellulitis never, ever goes to the bone. Unless there is a history of either bone fracture or chronic skin ulcer/trauma. I will have to add it to my list of medical absolutes.

Recurrent cellulitis: Group A Streptococcus from lymphedema. Always.

Rationalization

There aren’t any references because there has never been a case of osteomyelitis from cellulitis or recurrent cellulitis from osteomyelitis. With the caveats as noted.

Chapter One Hundred Five

Close. But no cigar.

Aug 22, 2015

Not that I smoke. But so often, I have a great diagnosis that is ruined by negative tests. If the Secret were real, I would be awash in great pathology, wishing making it so. No such luck.

The patient has had a prolonged chemotherapy-induced neutropenia for large B cell lymphoma and is admitted for fevers and respiratory failure.

The diagnosis of PJP was made, he was started on tmp/sulfa, and his WBC returned. Boy, did it return.

45,000. And it stayed up. So they called me.

The only other interesting abnormality was an increasing alkaline phosphatase. I thought for sure this was going to be hepatosplenic Candida. The beta-d-glucan is 450, but he has PJP, so that doesn’t count. It was, I said, textbook. Get an enhanced CT, and it will, will I tell you, show the focal defects of Candida.

It didn’t.

Hmmm. As my father used to tell me, get out. No. Before that. If the labs do not support the clinical diagnosis, then it is the labs that are wrong. Besides, I have had two cases of hepatosplenic Candida that were only positive in liver biopsy.

For maximum imaging sensitivity, patients should be studied with US and nonenhanced and enhanced CT. Even when both US and CT scans are negative, if there is a strong clinical suggestion of candidiasis, open biopsy is recommended.

And since she needs more chemotherapy sooner rather than later as this was the induction chemotherapy, we went for a liver biopsy.

Steatohepatitis. A disease that will not be treated with antifungals, so that was stopped.

Why the steatohepatitis? She is not a drinker and had no prior liver disease. Pubmed finds a smattering associated with lymphomas, so it may be due to the underlying malignancy.

Rationalization

Hepatosplenic Candidiasis in Patients with Acute Leukemia: Incidence and Prognostic Implications.

http://cid.oxfordjournals.org/content/24/3/375.full.pdf

Radiology. 1988 Feb;166(2):417–21. Hepatosplenic candidiasis: wheels within wheels.

http://www.ncbi.nlm.nih.gov/pubmed/3275982

Turk J Pediatr. 2014 Jul-Aug;56(4):399–403. Development of fatty liver in children with non-Hodgkin lymphoma.

http://www.ncbi.nlm.nih.gov/pubmed/25818959

POLL RESULTS

My father

• told me to get out. 27%
• took me aside. And left me there. 23%
• told me the 5 a's of a consultant: availability, ability, appearance, affability and accountability. 4/5 ain't bad 17%
• told me to get a pre-nup. 10%
• gave me a name. Then he walked away. 10%
• Other Answers 13%
  • told me “You underestimate the power of the dark side,”
  • wondered aloud if I thought that I were some sort of privileged character, and died from smoking Kents when he was 41. I was 11.

Chapter One Hundred Six

Not Positive

Aug 25, 2015

There is an art to some aspects of medicine. Reading a PPD is lost art in the US since there are so few positives to read. People measure the erythema, not the induration, and determining the borders of the induration is not always so clear cut.

The gram stain is also an art, both in preparation and reading. When I was an intern, back in a time before CTs and third-generation cephalosporins, we did our own gram stains, and my hands were always tinted purple by sunrise. It was a tricky procedure to get just right, and I was never very adept at seeing gram negatives against the pink background of pus.

Even trained professionals can have trouble reading a gram stain, so I do not feel too bad.

The patient had a craniotomy with a CSF leak that needed repair. He had no symptoms of infection at the time of surgery, and in the OR, the surgeon sent off a gram stain and culture even though it did not look infected. They do that on occasion, and I get to deal with the results.

So while there were no WBCs on the specimen, there was one plus gram-negative bacilli.

I looked at the time the gram stain was read. 5 pm. Aha. The A-team (the microbiologists) goes home at 4, and the stain had been read by the general lab tech.

It is not all the unusual for the night tech to overcall a gram stain. Better to call a positive that isn’t than a negative that is. If you know what I mean.

Gram precipitation is sometimes called gram-positive cocci on CSF, a false positive. A while back, there was a batch of swabs that contained dead gram-negative rods, leading to a false true positive !?!.

The rate per 1,000 smears showing nonviable Gram-negative bacilli (false-positive smears) increased from a baseline of 10.8 to 38.5 following purchase of new culture-collection devices; the rate decreased to 8.0 following replacement of contaminated culture sets. False-positive reports led to changes in therapy for five patients. In addition to being sterile, commercial culture-collection devices should be certified by the manufacturer as being free of stainable microorganisms or as unsuitable for preparation of Gram-stained smears.

There are a variety of other ways gram stains can be false positive, including bacterial contamination of reagents and supplies.

Nonviable gram-negative bacilli were found in 6.7% of manometers, and 23.3% to 90% of the specimen tubes tested from the same lots of commercial lumbar puncture trays. It was estimated that there were between 44 and 333 organisms per specimen tube. Two lots of the commercial myelogram trays yielded nonviable gram-negative bacilli from 50% of the specimen tubes and 33.3% of the manometers tested. Retrospective review of laboratory records for 1982 and 1983 revealed 23 total CSF smears positive for gram-negative bacilli. No CSF grew gram-negative bacilli, and chart reviews confirmed a diagnosis of factitious meningitis in each case.

Like all tests, the gram stain has to be interpreted in the context of a clinical scenario, and if the gram stain makes no clinical sense, question it.

One of my rules is any gram stain read after quitting time, especially if there is no purulence on the slide, is to have it re-reviewed by microbiologists. Part of the bummer of my hospital system is the central lab is in a different hospital, and I can no longer wander down and look at gram stain myself. It saves money to have one lab, but it does take away a bit of the hands-on fun of ID.

So I asked the lab to check it out: 2 said nope, just some red schmutz that looked roddy and one said maybe but she would not have called it.

So probably a false positive. But I will wait until the cultures are negative at 72 hours just to make sure.

Rationalization

South Med J. 1978 Dec;71(12):1524–5. Erroneous diagnosis of meningitis due to false-positive gram stains.

http://www.ncbi.nlm.nih.gov/pubmed/83006

Infect Control Hosp Epidemiol. 1988 Nov;9(11):501–3. Factitious meningitis: a recurring problem.

http://www.ncbi.nlm.nih.gov/pubmed/3225472

False Positive Gram-Stained Smears.

http://www.researchgate.net/publication/23052125\_False\_Positive\_Gram-Stained\_Smears

POLL RESULTS

I hate false positive

• gram stains 6%
• VDRL's, especially my own. 6%
• Lyme serolgies 30%
• IQ tests 24%
• Florida elections 30%

Chapter One Hundred Seven

The Worst Part of Being a Doctor

Aug 26, 2015

It is really hard to whinge about being a physician and not looking like the diminutive of Richard. My job and life are better than 99.9% of the world now and in the past. If I do my job right, maybe I save a life or relieve suffering. Even on the worst day, the world is (I hope) a little better for my having done my job.

Thirty plus years of acute care medicine have taught me that if my day is not a total inconvenient pain in the ass, then I am missing something important. Acute care medicine is chaotic and unpredictable, and it is an environment in which I am quite comfortable.

That is not to say I will not bitch about call or insurance or some of the stupid practices I see year after year. Really. You sent an MRSA bacteremia home on oral clindamycin? In 2015? You can’t even be bothered to read about it Up To Date? What a maroon.

I can get grumpy with the best of them, but at the end of the day, these are at best minor annoyances. Being an ID doctor in Portland has to be the best of all possible worlds that do not have issues with shrimp.

The worst part about being a doctor is not being able to help someone. Not reaching the end of available therapies or even having no therapy to offer because of the nature of the disease. That happens. While I may not be able to treat their disease, I can still help the patient and their family understand the process and what to expect.

The worst cases are those where I have nothing to offer, a complete blank. I have recently had a spate of these in clinic. The patients are ill; I almost never deny a patients symptoms. It may be a fatigue or pain condition, and they have been referred to me to find the reason. They have often had all the diagnostic tests imaginable when I see them. You know us ID doctors, we like a good diagnostic mystery. And the patient looks so hopeful that I will solve their mystery.

And I get done with the H&P, and I got nothing. No idea what they have except to say it is likely not infectious. I have no alternative diagnosis. No ideas for further diagnostic testing. No ideas for treatment. No nothing.

I have to tell the patient: I got nothing. No ideas. I haven’t a clue as to what you have or what to do about it. I am unable to bs them with some smoke and mirrors explanation. That, I suppose, is what CAM is for.

I feel an obligation to tell my patients the truth, and I try to be gentle, but so often their face falls, and they break into tears.

Expletive deleted.

For me, that is the worst part of being a doctor, being unable to help those who come to me for an answer.

The other aggravations that can make me grumpy during the day? Someone using antibiotics as if they were antipyretics? Filling out an insurance form? Sitting yet again on the I-5 to the I-84 interchange? Nothing really.

Rationalization

Shrimp worlds

https://buffy.fandom.com/wiki/Shrimp\_worlds

POLL RESULTS

The worst part about being a doctor is

• paperwork 35%
• I am not treated like the god I truly am 17%
• listening to those smug ID docs drone on about antibiotics. 4%
• spelling diseases and drugs 10%
• typing in the EMR. 23%
• Other Answers 12%
  • inability to help (as you eloquently said yourself)
  • On-call weekends
  • night work
  • I imagine, having patients who agree with you, but insist on not following your advice, which is supposed to keep them from dying.

Chapter One Hundred Eight

What's the diff?

Aug 28, 2015

The patient had bypass surgery, and for 48–78 hours post-op was hypotensive, pressor dependent, blue, and mottled.

Eventually, he recovered, blood pressure normalized, and he pinked up nicely.

And then the fevers and leukocytosis began.

We did the usual fever workup and found nothing of note, and I blamed it on reperfusion.

You see this on occasion if you watch for it. When ischemic tissue is reperfused patients will get a fever and a leukocytosis that lasts for five days or so. And the fever is often continuous, as in this patient. That is a clinical observation with no data to support it, and it may well be confirmation bias, but that is my story, and I am sticking with it.

Infarctions of tissue can also cause a fever. This has been described with dead tissue of all kinds: heart, liver, and brain. Or the spleen. Today I noted that he also has Howell-Jolly bodies and nucleated red cells on his differential in addition to the leukocytosis.

Hyposplenism may be obvious from the blood film with nucleated red cells, acanthocytes, target cells and Howell-Jolly bodies.

His creatine makes an enhanced CT problematic, but with the HJ bodies, I am blaming dead spleen for the fever.

This is the second or third time in the last year I have noted new HJ body’s post-op in a patient, and it was proven later that yes, indeed, the spleen was infarcted.

Chapter One Hundred Nine

The Girl With Empyema

Aug 31, 2015

Tall and tan and after a VATS

The girl with empyema goes walking

And when she breaths, each breath she passes

Goes “Arrgh”

When she breathes it's short and shallow

Air moves so cool and cough so gentle

And when she breaths, each breath she passes

Goes “Arrgh”

Oh, but I watch her so sadly

How can I tell her S. hominis?

Yes, nosocomia from VATS gone badly

But each day as she walks the hall

She looks at the chest tube, so as not to fall

Tall and tan and after a VATS

The girl with empyema goes walking

And when she breaths, each breath she passes

Goes “Arrgh”

Rationalization

Frank Sinatra – The Girl From Ipanema Lyrics

https://www.lyricsfreak.com/f/frank+sinatra/girl+from+ipanema+the\_10121534.html

The Girl From Ipanema

https://www.youtube.com/watch?v=09gJX0Cc6p0