I Have Returned

Sep 2, 2020

I had been gone from work for 12 days, our yearly summer vacation in Sunriver, Oregon. Three extra days this year, and it makes all the difference. To you young whippersnappers reading this, ID is great. Time off is even better. Don't pass it up. Remember, no one EVER said on their deathbed, "Doc, I sure wish I had spent more time at work."

Then, upon returning, I could not access the blog for more than a week. But, like MacArthur, I have returned, but with dry pants.

Still, I do like ID and medicine, and the return to work isn't all that bad. The toughest part of medicine is picking up a service of new patients who are well into their admission. After all these years, I never feel like I really know the issues like I do if I had been involved from the beginning. And I think the EMR makes it harder to pick up new patients as the chart is

Filled

With

So

Much

Extraneous

Worthless

Crap.

While I was gone the patient was admitted with fevers, shoulder pain, and 5 out of 5 positive blood cultures for MSSA, a consequence of IVDA.

She was evaluated with MRI and US and felt not to have a joint infection. When I see her, she can't do the chicken dance. I have mentioned the chicken dance before in relation to infected shoulders. It is a sign right up there with the speed bump sign as an indication of infectious pathology, although not worthy of Ig Nobel.

As usual, I declared that given S. aureus in the blood and the inability to move the shoulder, there had to be pus under pressure in or around the joint. As my father said early in my practice, if the tests do not support the clinical diagnosis, it is the tests that are wrong. Yep. My dad was, let us say, as sure of himself as I am.

And there was pus in the shoulder and surrounding tissues. MRSA can be quite extensive given a chance, but she improved with cold steel and antibiotics

The curious finding was blue sclera, and with direct questioning, she admitted that she had been hypermobile in her youth and had a lot of joint discomfort.

I thought I had discussed the possible relationship between Ehlers-Danlos Syndrome (EDS) and infective endocarditis (IE) before. Nope. It was wound infections and EDS. But there may be an association between EDS and IE.

Her evaluation to date does not find endocarditis, but I remain a Noland and Beaty kind of guy: community-acquired SAB with no source is endocarditis:

Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis.

I plan on having the reference engraved on my tombstone.

But I wondered if EDS was a risk for joint infections. Nope. At least not that is reported. I found that a surprise, given all the natural trauma to EDS joints, one would think they would be a set up for the occasional infection. But, as they like to note in the skeptical world, the absence of evidence is not necessarily evidence of absence.

Still, I wonder.

Rationalization

Chicken dance. https://www.youtube.com/watch?v=6UV3kRV46Zs

Speed Bump http://boards.medscape.com/forums/?128@@.2a8005e6!comment=1

Looking Is Not Seeing http://boards.medscape.com/forums/?128@@.2a82faa9!comment=1

Staphylococcus aureus bacteremia. Current clinical patterns https://pubmed.ncbi.nlm.nih.gov/1274983/

Ehlers-Danlos syndrome with infective endocarditis: A case report with literature review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322054/

Edzard Ernst: Absence of evidence is not evidence of absence https://blogs.bmj.com/bmj/2012/03/19/edzard-ernst-absence-of-evidence-is-not-evidence-of-absence/

Swarming Subdural

Sep 21, 2020

How long do you stay in a dysfunctional relationship? When do you say enough is enough? A divorce will not end the relationship; there are still the kids to consider.

The CDC, the FDA, the NIH? Sorry. At least with COVID, the relationship is over. Medicine is based on trust, and I can no longer trust any of you.

So while I can't wash my hands of you. Or socially distance. Or wear a mask. For COVID enough is enough. Time to move on. I need to be able to trust again.

The patient comes in with a day of headache, fevers, and a seizure. The evaluation shows a subdural empyema from mastoiditis.

That is bad. Really bad.

I think I have seen but one subdural empyema in my career, and it was at the beginning of the MRI era. Yes, I am old enough to remember a time before the MRI. In fact, when I say my first MRI, I thought it was a Netter-like pencil sketch; the detail was so remarkable. However, it is the best way to make the diagnosis:

The diagnostic procedure of choice for intracranial and spinal SDE is MRI with gadolinium enhancement.

And it is really an emergency, a drop everything and get it drained NOW

as the most imperative of neurological emergencies," which, if not treated immediately, is associated with high risk of status epilepticus, spreading cortical venous and cortico-venous sinus thrombosis, fulminating cerebritis, brain swelling, cerebral coning, and ultimately leads to death.

The microbiology is that of sinusitis; S. aureus, Streptococci, and/or anaerobes.

It is hard to say for sure as it is a rare disease and I could not access to all the literature, but for gram-negative rods, the two most common in subdural empyemas are Pseudomonas and Proteus mirabilis. The former doesn't surprise me, but the latter did.

Looking over the sinusitis literature, P. mirabilis is found in chronic disease occasionally, in single-digit percentages.

And it may be more common in mastoiditis:

Pseudomonas aeruginosa was the most frequent isolate (23.5 %). It was recovered from four patients (57 %). This organism was followed by Proteus sp. (17.6 %).

Although the number of patients in all these series are relatively small.

I mention it as P. mirabilis was the primary organism in the deep cultures of the empyema. I say primary, as it swarmed all over the plates. I asked the lab if there could be any other organism hidden in the mess of Proteus. Maybe, but too much swarming to tell. More superficial cultures had a more diverse microbiology, consistent with chronic sinusitis.

I have discussed swarming before, but it is still a pain as it can overwhelm other organisms, obscuring an accurate microbiologic diagnosis.

The patient survived, but long-term recovery is uncertain.

Rationalization

A Review of Subdural Empyema and Its Management https://journals.lww.com/infectdis/Fulltext/2007/05000/A_Review_of_Subdural_Empyema_and_Its_Management.6.aspx

Bacteriology of Chronic Sinusitis and Acute Exacerbation of Chronic Sinusitis https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/484545

A prospective study of seven patients with chronic mastoiditis Open Access https://www.microbiologyresearch.org/content/journal/jmmcr/10.1099/jmmcr.0.000079?crawler=true Swarm http://boards.medscape.com/forums/?128@@.2a7c8ec6!comment=1

In the age of the COVID-19 pandemic, can we trust the CDC and FDA any more? https://sciencebasedmedicine.org/can-we-trust-the-cdc-and-fda-any-more/ Nope. Now I will have to verify everything. Like I need more work.

Makeup

Sep 23, 2020

What is interesting and cool about ID is often the little things. So many infections result from human behavior: what you eat, where you go, what animals you have etc. I don't think the other medical specialties have those kinds of curiosities.

The patient comes in with recurrent MRSA boils. Nothing exceptional in the history, she has had 4 months of boils, and her kids have had them for about two months. No smoking gun as to a source, so I go through the routine of how to decolonize her family and environment.

I usually suggest patients toss all their makeup, creams, and ointments, and note if they touch their face, then touch the face cream, then, viola, the cream is contaminated.

As I talked, you could see the light come in her face as a realization struck.

Her sister, she said, had MRSA several months back and had put Vaseline on the infection, and her sister had given the same jar to her. The boils had started shortly after that. And, after using the Vaseline on her kids, they got boils.

Just how often are cosmetics a vector for MRSA? Years ago, we had an outbreak at one of my hospitals we traced to a multi-use Johnsons Intensive Care pump bottle on a nursing station. It was culture-positive, and once we tossed it, the outbreak stopped.

So I am leery of makeup and suggest MRSA patients go without for two weeks and start with new product after decolonization. Kind of like the news anchors in Batman.

But how often does it happen?

To my surprise, I couldn't find much.

There is a small study that suggests cosmetic use may increase the risk of MRSA:

We isolated Coagulase Negative Staphylococci (CoNS), Micrococcus spp. and methicillin sensitive S.aureus, non-fermenting oxidase negative gram negative bacilli and diphtheroids from both the groups. We found that most of the students who were regular cosmetic users 22 (52.38%) yielded negligent growth in comparison with non-cosmetic users (16, 38%). CoNS was less frequently isolated from regular cosmetic users 10 (23.8%) in comparison with those who do not use cosmetics 17 (40.47%).

And cosmetics support the growth of Staphylococci:

This study was conducted using 55 samples representing 19 types of cosmetics, divided into three groups: used by one person, used by several people and after the expiry date. In cosmetic samples the general numbers of aerobic mesophilic bacteria were determined with the spread plate method on tryptic-soy agar. The presence of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans were also checked. Results. The number of aerobic mesophylic bacteria in the tested cosmetics ranged from the level below the method detectability to 1.3×107 cfu/g or ml. The presence of Staphylococcus spp. was found in 11 (20.0%) tested cosmetic samples and of P. aeruginosa in one tested preparation.

There are no transmission by a cosmetic vector on Google Scholar or the Pubmeds. An outbreak in a prison found

... that sharing personal hygiene items is a risk factor for MRSA infection is consistent with these observations.

But they did not credit a specific product beyond soap. The closest I could find was a newspaper report where

"The only thing we can put it down to is the makeup brush," she told the paper. "My friend did have a staph infection on her face, and I was using her brush just before. I had no idea that could even happen, I used to share with my friends all the time."

And the makeup departments at the mall?

'Disgusting'. Charlotte-area makeup testers contained MRSA, E. Coli and more, doctor says.

I still bet MRSA is spread or perpetuated by cosmetics.

And Vaseline.

Rationalization

Joker's Brand New Product! Smylex https://youtu.be/cROY4m4Ftiw

In Batman (1989) the news anchors stop wearing makeup after the Joker poisons beauty hygiene products in Gotham. https://imgur.com/r/imagesofthe1980s/2TWlLs0

Comparison of Normal Resident Flora on the Face of Medical Students who use and who do not use Cosmetics. http://dx.doi.org/10.7860/JCDR/2017/28907.10789

[Microbiological purity assessment of cosmetics used by one and several persons and cosmetics after their expiry date http://agro.icm.edu.pl/agro/element/bwmeta1.element.agro-adc4010b-c19d-42be-a0a3-2b9b4f8ff982)

Infection from makeup brush leaves young mom paralyzed https://www.cbsnews.com/news/infection-from-makeup-brush-leaves-young-mom-paralyzed/

Personal Hygiene and Methicillin-resistant Staphylococcus aureus Infection https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291434/

'Disgusting' | Charlotte-area makeup testers contained MRSA, E. Coli and more, doctor says https://www.wcnc.com/article/news/investigations/defenders-team-finds-mrsa-e-coli-herpes-and-more-on-charlotte-area-makeup-testers/275-612c5348-80d2-4bfc-9c20-db3ac805e2c3

POLL RESULTS

I worry about infections spread by

• makeup 5%
• toilet seats 5%
• stupidity 76%
• mal aria 3%
• beer. Now that would be hell. 11%

Luke O'Cytoclastic-The Irish Vasculitis

I'm back. Nope. No COVID 45. Yet. First, the blog had issues, and I couldn't post. Then, just as the blog was repaired, I went on an extended vacation, circumnavigating the Olympic Peninsula and then heading over to Mt. Rainer. Amazing hiking. Saw bear and elk and otter and eagles and tremendous scenery. I love doing ID, but there is so much more in the world. As I have said before, no one has EVER said on their death bed, "Doc, I wish I had spent more time at work."

But I still need to work, mostly for health care benefits. I made the mistake of marrying a younger woman; she is 61 to my 63 and retired. So I need to work until she is Medicare eligible. But at least it is always fun and interesting.

The patient is found down in an alley. Homeless and unconscious, she is admitted with sepsis and a rash.

I find verbal/written descriptions of rashes to be worthless. Maybe it is helpful for a dermatologist, but I need a picture; worth far more than a thousand words.

Oct 12, 2020

So take a moment and click to see what I saw, then come on back. It looked just like this, on the legs, arms and some on the abdomen.

The examination is interesting, and there is are no lesions on the soles, palms, and conjunctiva to suggest these are embolic, especially as the patient has a vegetation on both the mitral and tricuspid valve.

So it is a leukocytoclastic vasculitis. But from? Blood cultures grow MRSA. It has been a long time since I have seen MRSA cause a leukocytoclastic vasculitis. It happens, albeit rarely.

This presentation represents an unusual case of biopsy-proven leukocytoclastic vasculitis that developed concomitantly with MSSA bacteremia and resolved with cephalosporin treatment.

To my surprise, there was only one case on the PubMeds, but I would bet I have seen a few more cases than that in my career, maybe one a decade. Although there are a pair of cases of S. aureus causing a

bacterial endocarditis associated with both pANCA and anti-MPO specificity that fulfilled definitions for systemic necrotizing vasculitis.

I more often see this disease as a complication of antibiotics, not infections. And there are a variety of other infections that lead to the process.

Post-infectious leukocytoclastic vasculitis is most commonly seen after streptococcal upper respiratory tract infection. Other infectious triggers include, but are not limited to, Mycobacterium, Staphylococcus aureus, Chlamydia, Neisseria, and HIV. Chronic infections with hepatitis B, hepatitis C, and syphilis can be associated with leukocytoclastic vasculitis as well.

And are a variety of other non-infectious i.e., uninteresting diseases that cause leukocytoclastic vasculitis as well.

With time and antibiotics, the leukocytoclastic vasculitis should improve. It did.

Rationalization

Staphylococcus aureus Bacteremia Masquerading as Leukocytoclastic Vasculitis https://www.amjmed.com/article/S0002-9343(15)01105-5/fulltext

Microscopic polyangiitis following recurrent Staphylococcus aureus bacteremia and infectious endocarditis https://pubmed.ncbi.nlm.nih.gov/17207390/

Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis) https://www.ncbi.nlm.nih.gov/books/NBK482159/

POLL RESULTS

I wish I had spent more time - at work 7% - at home 10% - drunk 10% - away from the internet 34% - ignoring the haters 28% Other Answers 10% - sex sex sex - focusing on what matters, or even having a clue.

Low Torque

Oct 14, 2020

The patient is a renal transplant seen in the outpatient clinic with a non-focal fever for three weeks.

I do the usual FUO history and nothing of note. Physical normal. Routine labs are normal.

I look for the usual OI's associated with renal transplantation and find nothing. No CMV,EBV, Cryptococcus.

Panscan? No pathology.

So, as a last test, I sent off the Karius test. And while we awaited the results, he got all better.

It is positive for Torque Teno virus, 5300 organisms. Now what?

I know I had read about this virus somewhere but remembered nothing.

The name? Per the Wikipedia

Initially the virus was named TTV after a patient with T.T. initials. Later the name torque (necklace) teno (from Latin tenuis - "thin") virus was adopted as it preserved the original abbreviation.

or more specifically

A tightly braided necklace or collar, often made of metal, worn by various early European peoples.

Thin necklace. It is pronounced 'tork', not tor-kay.

It is a circular single-stranded DNA. Who cares. It is de rigueur to mention the kind of nucleic acid configuration when discussing viruses, but outside of influenza and HIV, I can't see where it adds any useful information about understanding a virus.

Torque Teno is a ubiquitous virus, with up to 90% having the virus, and persistent viremia is common. It is often acquired in the first year of life.

And

is apparently ubiquitous in European wild boar populations.

And sausages. There are strains in other animals like chickens, pigeons, rats, lemurs, and house shrews, among others.

It is not associated with any disease; maybe Kikuchi-Fujimoto disease in some people; it does cause a necrotizing lymphadenitis in pigs.

In transplant patients, there is research using it as maker of immunosuppression, but

it remains to be shown if TTV is an accurate marker of level of immune suppression, or if TTV is a predictor of complications such as infections or rejections.

So. Was it the cause of the FUO? I don't think so. It was likely a serendipitous finding.

Rationalization

Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation. https://www.sciencedirect.com/science/article/pii/S0955470X19300059

Torque teno virus (TTV) is highly prevalent in the European wild boar (Sus scrofa) https://www.sciencedirect.com/science/article/pii/S0378113506002951

Torque teno virus dynamics during the first year of life https://pubmed.ncbi.nlm.nih.gov/29843750/

Strong association of Torque teno virus/Torque teno-like minivirus to Kikuchi-Fujimoto lymphadenitis (histiocytic necrotizing lymphadenitis) on quantitative analysis https://pubmed.ncbi.nlm.nih.gov/31782015/

Global impact of Torque teno virus infection in wild and domesticated animals https://pubmed.ncbi.nlm.nih.gov/26142664/

Itchy Nose

Oct 19, 2020

My son saw a round piece of copper on the kitchen counter and picked it up.

He looked at the pin and noted it said, "IDSA. COVID 19 Response."

What's this? he asked. An award?

No, I said. The IDSA sent it to every member.

That, he said, Is the stupidest thing I have ever seen.

I could not disagree. Why spend thousands of dollars to design, produce, and send a chunk of metal to all the Society members? With the resultant carbon footprint for something that no one needs? And I assume they spent my dues money to make it.

I mean, if you are going to spend my dues, spend it on vaccinations or buying food for the hungry who have lost jobs due to COVID. Help someone, don't piss away money on the useless brick-a-brack.

I think the archaic NEJM mouse pad, sent in bubblewrap no less, is stupider, but only by a hair.

With the pin was a card that noted the IDSA is here to serve me. Oh yeah? Then why have you ignored several emails asking where the electronic version of CID is? Too busy frittering away funds on commemorative pins, I guess. From mousepads to plastic-covered journals to useless chunks of metal, my professional organizations continue to disappoint.

The patient is a middle-aged male who, for the last decade, has had unilateral recurrent tingling/itchy feeling inside his nose every couple of months for the last year. The nose feels like it is swollen but isn't.

That's really it.

Past medical history is negative, nothing odd. He came to see me as I had seen taken care of an unrelated infection several years back, and he wondered if I had any ideas.

Well, there is really only one infection that returns periodically, and that is Herpes. Ever had it?

Nope?

Your spouse?

Nope.

That means little. Most people with HSV have never had symptoms.

During 2015 2016, prevalence of herpes simplex virus type 1 (HSV-1) was 47.8%, and prevalence of herpes simplex virus type 2 (HSV-2) was 11.9%.

and

Oral herpes infection is mostly asymptomatic, and most people with HSV-1 infection are unaware they are infected.

So I checked serology, and HSV-1 was positive. The titer was quite high, as if it was being boosted.

There are cases of HSV-1 involving the nose, and there can be asymptomatic shedding;

HSV DNA was detected from tear samples in 3 (0.85%) swabs and nares in 12 (3%) swabs

He had never noted an intranasal lesion, but the inside of the nose is hard to see, and at best, can be examined only halfway to the first knuckle.

I can find no cases on the PubMeds or the Googles reporting recurrent HSV presently as pain/itching/tingling without ulcers. It is reported with VZV, however. But it seems a reasonable explanation.

We talked about the pros and cons of suppressive acyclovir, but the tingling is bothersome enough he wanted to give it a try.

So far, so good.

Rationalization

Prevalence of Herpes Simplex Virus Type 1 and Type 2 in Persons Aged 14 49: United States, 2015 2016 https://www.cdc.gov/nchs/products/databriefs/db304.htm

Herpes simplex virus https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus

Herpes Simplex Virus Type 1 Shedding in Tears, and Nasal and Oral Mucosa of Healthy Adults https://pubmed.ncbi.nlm.nih.gov/27835628/

POLL RESULTS

I will wear my IDSA COVID pin

• proudly 8%
• ironically 8%
• with deep embarrassment 8%
• in place of an ear ring 8%
• as far as the recycling bin 62% Other Answers 8%
• insist on recycling for cash from your local metal collector

I Don't Know Everything

Well, you knew that. You can't know everything. Medical knowledge is gained from reading the literature but, more importantly, combined with experience. Like any skill, the more you do it, the better you become.

Except for golf. I have played golf for maybe 55 years, and my game has been approximately the same since I was 16. With golf, practice makes mediocre.

There are many infections I simply never see and are rare enough that they never come up in the random reading of my feeds and subscriptions.

But once an odd infection is diagnosed, send them to ID. So I get odd cases about which I know absolutely nothing. Good thing, I am a quick study, and we have the Googles.

The patient comes to the clinic with the diagnosis of spirochetal colitis. Never heard of it. You?

History is straightforward. Routine screening colonoscopy made the biopsy. The patient has no medical problems and has no gi symptoms whatsoever.

There are 4 spirochete families, fewer than the mafia, and I had heard of the first three: Treponema, Borrelia, Leptospira and Brachyspira.

The most important one is

Brachyspira hyodysenteriae, the agent of swine dysentery, which induces an extensive and severe mucohaemorrhagic colitis in growing pigs.

Although there are six other named Brachyspira. Some cause disease in dogs, cats, opossum, non-human primates, and guinea pigs as well.

B. pilosicoli is a colonic pathogen of pigs and chickens and has been spread to humans, where it and Brachyspira aalborgi are the most common, found in anywhere from 28 to 100% of people.

In many cases, the histological findings of IS are simply an incidental discovery during a screening colonoscopy. Symptomatic IS is most commonly accompanied by complaints of chronic (watery) diarrhea and vague abdominal pain without other apparent cause.

Currently, the only way to make the diagnosis is on biopsy, so not helpful for the run-of-the-mill diarrhea.

Treatment is metronidazole (it is an anaerobe) but

Although treatment with effective antibiotic does lead to symptomatic remission and histological clearance in some patients, it is still uncertain whether it was the elimination of the spirochetes that led to the symptomatic improvement. Yet, other patients have no symptomatic relief with treatment despite clearance of spirochetes.

Since my patient had no symptoms, we elected not to treat. He was happy with that approach.

PS

If you are reading this, I keep having issues with the blogging platform and this one, obviously, was successfully posted. Keep checking back; one day it will get fixed. As Barbie said, "The internet is tough."

Rationalization

Spirochaetes as intestinal pathogens: Lessons from a Brachyspira genome https://gutpathogens.biomedcentral.com/articles/10.1186/1757-4749-1-10

Potential for Zoonotic Transmission of Brachyspira pilosicoli https://wwwnc.cdc.gov/eid/article/12/5/05-1180_article

Human intestinal spirochetosis -- a review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830567/

It is Quiet...Too Quiet

Oct 28, 2020

Before fall brings rains to the Great Pacific NW, we have been getting a lot of hiking in. Two weeks in and around the Olympic Peninsula and a pair of lovely hikes in the Willamette Valley forests last weekend.

One of the aspects I really like about the forests is the quiet. But it has been quiet this year. Too quiet.

Almost no birds in the forest. The number of seabirds, like plover, running along the sands seems down.

No birdsong. I don't think I was awakened once this summer by early morning birdsong. The Jays and Robins in my neighborhood are few and far between compared to what I remember when we moved in, where the Stellar Jays seemed to believe they owned the land my house is on.

No bugs. There are some insects flittering about, but not what I remember. The windshield splatter is rare. Looking at the forest surface, no ants or centipedes or other bugs.

There even seems to be a lack of mosquitos. I always hike along or to water and carry Off. This year we didn't need to use Off once.

The forest seems empty of the smaller creatures.

I know insect populations are plummeting. Although I can't find information as to whether mosquito populations are declining. All I can say is they have not been an issue hiking or sitting on my front porch this year.

I know that bird populations are declining as well.

And I remember reading that tropical rainforests are disturbingly quiet as the animals and insects vanish.

But I didn't think it had affected the NW forests.

Of course, it could just be my imagination/faulty memory. I just do not remember the forests being so empty of sound and small creatures.

So what difference does that make for an ID doctor?

Last month I had a pair of consults for encephalopathy/meningitis. The question I was asked was, what is the cause? Should West Nile be in the differential?

West Nile has been rare in Oregon. Even during the Great Recession, which led to an increase in West Nile in California, it didn't increase cases in Oregon because we have no pools. So I do not expect the current economic meltdown to increase West Nile in Oregon. Whether California needs to beware, I do not know.

I wondered if birds and mosquitos are dying off, shouldn't there be less West Nile. Is there? I can't tell from the data. Maybe 2020 has been quiet for West Nile in humans, birds, and mosquitos. Maybe not.

As is usually the case of CNS infections, no diagnosis was found, although both were negative for West Nile.

As the world heats up, it will change the epidemiology of infections as vectors die off or change their ecological range. Maybe West Nile will go away with the birds and mosquitos. But mosquitos are hardy and flexible insects. I bet they, along with cockroaches, will survive long after we have become extinct.

And live in a quiet world.

Rationalization

Delinquent Mortgages, Neglected Swimming Pools, and West Nile Virus, California https://wwwnc.cdc.gov/eid/article/14/11/08-0719_article

Preliminary Maps & Data for 2020 https://www.cdc.gov/westnile/statsmaps/preliminarymapsdata2020/index.html

It's Quiet& Too Quiet https://tvtropes.org/pmwiki/pmwiki.php/Main/ItsQuietTooQuiet

POLL RESULTS

As the world heats, I expect

• less West Nile 0%
• less RSV 0%
• more some things, less than others 38%
• fewer hoaxes like COVID 10%
• the unexpected 52%

Tell Med About the Rabbit Urine

Nov 3, 2020

Recently I needed to prescribe a course of erythromycin ethylsuccinate, EES. The drug is older than I am, so I figured it would be around 4 bucks. Off by a factor of 100. 400 bucks for the generic. And GoodRx says the average retail price is \$328.67. The brand name is about 100 bucks more. Amazing.

Anyway.

The patient is seen in the clinic, and EPIC says a blood and body fluid exposure. Been there, done that.

I expect this would be a work-related exposure, but a quick review says the exposure was a rabbit. Most of the records are not available as the patient had been evaluated in a system that doesn't link with EPIC.

A rabbit. Tularemia? Hepatitis E? Those are the infections I can think of. A Google suggested MAI, Pasturella, and Cryptosporidiosis, and for wild rabbits, plague, Salmonellosis, and Campylobacterosis should be on the list.

So I was somewhat ready when I saw the patient. Nope.

The baby rabbit was from a pet store, and after owning the rabbit for a month, it developed head tilt.

Head tilt? In humans, it is called torticollis, and one of the causes in rabbits is Encephalitozoon cuniculi. E. cuniculi is a massive issue in rabbits, with 80% seropositivity rates, most of whom are asymptomatic. In a minority, it causes renal and neurologic disease, including heat tilt, both of which this rabbit had. And the vet diagnosed the rabbit with E. cuniculi.

The exposure? While lifting the rabbit, it urinated in the eye, which was rinsed immediately. The eye, not the rabbit. So is there a risk from the E. cuniculi?

E. cuniculi is primarily excreted in rabbit urine, so in theory, yes. E. cuniculi is found in at least 20 other animals, and there are three types, so it is likely a zoonosis

In humans, E. cuniculi causes disseminated and neurologic disease in HIV and other similarly immunoincompetent patients; my patient is immunologically normal, and the exposure was 6 weeks ago.

The E. cuniculi was present and widespread among healthy rabbits (18.76%) and humans (9.76%) in China.

But the study doesn't discuss the direction of spread. One review notes

Direct transmission of this parasite from rabbits to humans has not been reported, but there is also no evidence that it can't be transmitted from rabbits,

The best that can be said is

However, it has been shown that E.cuniculi strains of human origin can infect rabbits and that the human strains isolated from AIDS patients are immunologically and molecularly identical to those isolated from rabbits. From this evidence it seems highly likely that E. cuniculi found in rabbits does pose a zoonotic risk to immunocompromised humans.

and

Chronic infections caused by E. cuniculi in immunocompetent individuals are generally asymptomatic, probably reflecting a balanced parasite-host relationship. E. cuniculi represents the vast majority of the microsporidial species found in the healthy population in the Czech Republic. A competent immune response is unable to eliminate fully the infection even if there are no clinical signs and the carrier can be a source of infection.

So there was a risk, probably very small, of E. cuniculi acquisition, and a zero chance of symptomatic disease. The bigger risk was likely the routine handling of the rabbit. And they had a dog, which could also be a source of E. cuniculi.

Since it was 6 weeks since the exposure and there were no symptoms, I figured the proof was in the pudding. No transmission had occured.

Rationalization

Zoonoses Associated with Rabbits https://iacuc.wsu.edu/zoonoses-associated-with-rabbits/

Worms and Germs https://www.wormsandgermsblog.com/wp-includes/ms-files.php?file=2008/04/M2-Rabbits-DVM.pdf

Head Tilt (Torticollis) in Rabbits: Don't Give Up http://www.bio.miami.edu/hare/tilt.html

POLL RESULTS

I try to avoid

• rabbit urine 24%
• aerosolized rabbit 47%
• raw rabbit 6%
• rabbit stool 12%
• rabbit feet 6% Other Answers 6%
• rabbit costumes

Intermittent Progression

Nov 5, 2020

The patient has been on treatment for myeloma with therapy that includes dexamethasone, 40 mg every week or so. He has a failed autologous stem cell transplantation.

Six months ago, he became fatigued, with intermittent, progressive dyspnea and a 50-pound weight loss.

The dyspnea pattern was interesting. He felt better for a day or two on the dexamethasone, then slightly worse than the prior week.

Finally, he was admitted, and I was called.

The exam was significant for marked cachexia. The LDH was 453. Albumin 1.8. The CXR had diffuse interstitial infiltrates.

The diagnosis was easy. It had to be PJP, and it was. The beta-D-glucan was > 500, and he got all better on a course of TMP-Sulfa.

PJP happens with myeloma; I remember at least one other case. How often?

The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in 3 categories: 1) high risk (incidence rates >45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; 2) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and 3) low risk (\<25 data-preserve-html-node="true" cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma.

In myeloma, bortezomib is a risk for PJP as well as dexamethasone. He was not on bortezomib. But intermittent steroids are a risk, especially in those with hematologic malignancies.

PCP diagnosis in the HIV-negative population requires a high level of suspicion even if patients are not receiving daily corticosteroids.

His protein malnutrition may have played a role. Not usually a risk in the US, historically it was a significant risk for PJP, usually in children with kwashiorkor.

The role of protein-calorie malnutrition in Pneumocystis carinii pneumonitis was explored with comparative studies in man and animals. Collective data from 225 cases of P carinii pneumonitis revealed mean body weights and serum protein values that were below normal. In matched comparison of 44 children with cancer and P carinii pneumonitis, serum albumin values and body weights were significantly lower than those of 44 patients with malignant neoplasms of the same type, duration, and therapy, but who did not have pneumonitis. Of 39 South African children who died with kwashiorkor, three (7.7%) were found to be infested with P carinii, whereas no organisms were found in the lungs of 21 well-nourished and geographically matched children. In Sprague-Dawley rats fed a 23% protein diet for normal growth, none of 15 acquired P carinii; whereas, 13 of 15 fed a protein-free diet died infested with P carinii.

And as long as we are on the topic of PJP, I have been annoyed for years by the lack of data to guide PJP prophylaxis in patients whose risk is that they are only on steroids. Outside of dexamethasone, I have never (that I can remember) had a case of PJP from prednisone alone.

Finally, a study. PJP occurred

in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent).

and

Of confirmed PCP cases, 79.0% developed pneumonia within 6 months of starting glucocorticoid therapy, with 86.0% developing pneumonia within 1 year.

Although the population was 716 patients admitted with pneumonia, so we still do not have great data on the risk of populations on steroids---mostly opinions.

There are no guidelines or randomized clinical trials for PCP prophylaxis in patients who do not have HIV and who are managed on long term steroids. However, the American Thoracic Society provides a low evidence-based recommendation to consider PCP prophylaxis during the time period of treatment with >20 mg/day of prednisone for longer than 1 month.

But an opinion that now has a bit of data to support it. And perhaps prophylaxis is the safer approach.

The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17--226)) was lower than the number needed to harm by serious ADR (45 (15--∞)).

Rationalization

Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients https://pubmed.ncbi.nlm.nih.gov/25058862/

Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patient https://www.hindawi.com/journals/crj/2016/2464791/

Protein-Calorie Malnutrition A Host Determinant for Pneumocystis carinii Infection https://jamanetwork.com/journals/jamapediatrics/article-abstract/505587

Aetiology and prognostic risk factors of mortality in patients with pneumonia receiving glucocorticoids alone or glucocorticoids and other immunosuppressants: a retrospective cohort study https://bmjopen.bmj.com/content/10/10/e037419?rss=1

Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids---clinical implication of primary prophylaxis using trimethoprim--sulfamethoxazole https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1996-6

[When to Initiate PCP Prophylaxis in Patients Managed on Long-term Steroids] (https://www.pharmacytimes.com/contributor/alexander-kantorovich-pharmd-bcps/2018/08/when-to-initiate-pcp-prophylaxis-in-patients-managed-on-long-term-steroids)

Focused on the Wrong Labs

Nov 9, 2020

The patient was admitted to Another Hospital with pneumonia. Radiographically, it was odd: one large peripheral round infiltrate, about the size of a lemon, and a smaller satellite lesion, about the size of a key lime. For those who are not cooks or bartenders, a key lime is smaller than the usual Persian lime.

As she had a hematologic malignancy, she had a bronchoscopy that grew Aspergillus, a galactomannan ratio of 1.58, and a beta D glucan >

500. She was started on voriconazole and discharged.

Two weeks later, she was admitted to my hospital with the infiltrates larger and starting to maybe cavitate. I was consulted.

I was skeptical of the diagnosis. The culture was one colony of Aspergillus versicolor, not a common pathogen. One colony of any Aspergillus should be approached with a grain of salt substitute, as it likely drifted in the air and onto the plate.

And the CT didn't look like Aspergillus. No cavity.

So why the elevated beta D Glucan? Another fungus? Maybe. But no risks and, again, it didn't look right. It looked more like Nocardia to me, and she was a gardener. Regular readers are aware that this blog contains 3/5ths of the cases of Nocardia with elevated beta D Glucan. But how about the elevated galactomannan assay? The title says it all: False-positive galactomannan antigen testing in pulmonary nocardiosis.

We need more specimens, I said. We need to send for Nocardia cultures. And if the Aspergillus is real, we need it for susceptibility testing as it is progressing on voriconazole. As best I can tell, this mold has variable susceptibilities to antifungals, although the numbers are small.

Add Nocardia therapy. Oh. And add azithromycin. After the patient had been discharged, her Legionella PCR was positive, and the urine antigen was negative, and it was not noticed/treated. We have to treat non-pneumophilia Legionella. I can't put it all together. Legionella doesn't cause positive fungal assays that I can find. And, as the patient was doing poorly, I sent off a Karius test to hedge my diagnostic bets.

The results of the second bronchoscopy: no mold isolated. No galactomannan was measured. No Nocardia. But the Karius showed lots of Legionella micdadei DNA.

So it looks to all be Legionella micdadei, which is consistent with the clinical course if you ignore the fungal antigens, which was the diagnostic hinge-point I put too much emphasis on, although I did not ignore the Legionella. Whew.

What looked to be early formation of a cavity may be a feature of Legionella micdadei:

Unusual features included dual infections in three patients and pulmonary cavitation in five patients.

Although I have it my brain Legionella micdadei cavitates late in the clinical course of the disease, I can't find the reference.

Over the last couple of years, I have become more uncertain about what to make of beta D glucans. So often it is up, > 500 up, when I can't find a reason, infectious or otherwise.

To make the case all the more confusing, both bronchoscopies grew an Enterococcus that I ignored. Enterococcus is not a cause of pneumonia. Well, it does, but it is rare. I have never had a case I can remember.

And it doesn't cause elevated fungal antigens this high. Maybe

... patients with Enterococcus faecalis bacteremia had significantly higher BDG levels than patients with bacteremia of other origins (135 pg/ml versus 15 pg/ml; P = 0.04).

She was improving symptomatically on anti-Legionella therapy but succumbed to complications of her malignancy.

In the end, I never felt like I understood the case. To paraphrase Barbie, ID is tough.

Rationalization

False-positive galactomannan antigen testing in pulmonary nocardiosis https://doi.org/10.1093/mmy/myaa084

Invasive pulmonary aspergillosis caused by Aspergillus versicolor in a patient on mechanical ventilation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562921/

A Comparative Study of Legionella micdadei and Other Nosocomial Acquired Pneumonia https://www.sciencedirect.com/science/article/abs/pii/S0012369215403770

[Enterococcus faecium lung abscess: one case report and literature review] https://pubmed.ncbi.nlm.nih.gov/20367948/

POLL RESULTS

Barbie had it easy, although

• math class is tough 6%
• ID is tough 6%
• medicine is tough 18%
• Ken is wimp 41%
• she hates it when shrimp is thrown on her 29%

Return to the Beginning

Nov 11, 2020

The patient, with no medical problems, is accidentally bit by his dog. He presents febrile and in shock.

The exam has purple fingers and toes. Platelets are 10. Hgb is 8, the LDH is 753, and there are lots of schistocytes on the smear.

It looks more HUS/TTP than purpura fulminans.

I mention that as the classic catastrophic consequence of a dog bite is purpura fulminans from Capnocytophaga canimorsus, although usually, but not always, in asplenics.

Two cases of infectious purpura fulminans and septic shock caused by Capnocytophaga canimorsus transmitted from dogs.

Hint hint, that is often a board question.

Does Capnocytophaga canimorsus cause HUS/TTP? Besides E. coli, the only bacteremia I knew associated with HUS/TTP is S. pneumoniae. The mechanism is understood but not remembered by me.

These clinical isolates of HUS pneumococci efficiently bound human plasminogen via the bacterial surface proteins Tuf and PspC. When activated to plasmin at the bacterial surface, the active protease degraded fibrinogen and cleaved C3b. Here, we show that PspC is a pneumococcal plasminogen receptor and that plasmin generated on the surface of HUS pneumococci damages endothelial cells, causing endothelial retraction and exposure of the underlying matrix.

In one ear, out the other. If you are really interested, see the reference below.

A quick search shows Capnocytophaga canimorsus does indeed cause HUS/TTP. So the patient is treated with antibiotics and plasmapheresis.

And the next day, gram-negative rods are growing in the blood cultures. But growing poorly. Three days later, no answer. I called the lab. Thin, pointy gram-negative rods are growing anaerobically. Could it be Fusobacterium? Another search finds Fusobacterium is also associated with HUS/TTP, albeit much less frequently. And Fusobacterium are also in dogs' mouths.

But then the next day, the MALDI-TOV calls it a Vibrio. Say what? It is a pointy gram-negative rod but NOT associated with dog bites, HUS or TTP. And no real risks for a Vibrio infection. Confirmatory tests make it less likely it is either Capnocytophaga canimorsus or Vibrio. But I treat them all.

But what was it?

Finally, it grew enough to re-evaluate, and the MALDI this time calls it? Capnocytophaga canimorsus. The other tests were off, the lab tells me, likely due to technical issues.

There are many other organisms associated with HUS/TTP and include: S dysenteriae, Salmonella typhi, Campylobacter jejuni, Yersinia pseudotuberculosis, Neisseria meningitidis, Legionella pneumophila, Mycoplasma, Rickettsia, Human immunodeficiency virus, Coxsackievirus, Echovirus, Adenovirus, Influenza virus, Epstein-Barr virus, and Herpes simplex virus.

Quite the list.

Rationalization

Two cases of infectious purpura fulminans and septic shock caused by Capnocytophaga canimorsus transmitted from dogs https://pubmed.ncbi.nlm.nih.gov/22497463/

Streptococcus pneumoniae-associated hemolytic uremic syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904394/

Hemolytic Uremic Syndrome Associated With Pneumococci in Children---An Elusive Mystery Now Explained? https://academic.oup.com/jid/article/217/3/341/4095067

Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite. https://pubmed.ncbi.nlm.nih.gov/10352221/

Hemolytic uremic syndrome in an adolescent with Fusobacterium necrophorum bacteremia https://pubmed.ncbi.nlm.nih.gov/11228199/

Atypical Hemolytic--Uremic Syndrome https://www.nejm.org/doi/full/10.1056/nejmra0902814

Resisting Temptation

Nov 17, 2020

The patient presents with periorbital cellulitis that progresses to severe eye pain and proptosis. CT shows, among other things, a thrombosed right superior ophthalmic vein. This, as you may remember (I didn't), feeds into the cavernous sinus. Blood cultures grow MRSA, and she is started on vancomycin. I am called to see the patient.

There are a few similar cases on PubMed, some with problematic results.

An illustrative case of septic superior ophthalmic vein thrombosis secondary to a staphylococcus orbital cellulitis is presented and correlated with autopsy findings.

The first thing I did was get the patient off vancomycin. I have concluded that vancomycin should be limited to infections where there is excellent source control. Otherwise, given the poor penetration of vancomycin into almost every body space or body part, I go with ceftaroline or daptomycin. I fully admit this is bias, not really supported by clinical trials that show mostly equivalency of all the MRSA antibiotics. I have had too many failures with vancomycin that I let my confirmation bias run free. Vancomycin isn't a big gun; it's a wet cap pistol.

And, giving in to my pharmacokinetic urges, I went with high dose (q 8) ceftaroline; again, I was hoping for better penetration into the clot. "Think pharmacokinetically, dose accordingly" is my motto.

Then I fretted about the clot. The other name for S. aureus is coagulase-positive Staphylococcus. S. aureus coagulase, and other proteins, are potent blood clotters. In 1904 it was first noted that

the staphylococcus seems to have caused the coagulation of the blood inside the animal body.

Ick.

The patient was placed on heparin, but should I mess with the production of coagulase with clindamycin, rifampin, or linezolid? I am a fan of messing with the production of bacterial virulence factors, if possible. There are macrolides to prevent toxic shock toxin production. And probably for PVL producing Staphylococcal lung infections.

I have debated inhibiting coagulase production for S. aureus epidural abscesses, as I have seen a couple of vertebral artery thromboses leading to acute transverse myelitis. But I have never done it.

I went looking again and found a lot of interesting papers, all in vitro or animal models:

In vivo studies also support the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization in the management of toxin-associated staphylococcal diseases and offering a potentially valuable strategy to improve patient outcomes.

But nothing I could find about using antibiotics to block coagulase production. So I didn't. But I remain sorely tempted by the concept.

Rationalization

Septic superior ophthalmic vein thrombosis https://pubmed.ncbi.nlm.nih.gov/11886421/

Outcomes of Ceftaroline Fosamil q8h vs. q12h Dosing Frequency for High-Burden, Gram-positive Infections https://academic.oup.com/ofid/article/4/suppl_1/S545/4295907

Staphylococcus aureus Secretes Coagulase and von Willebrand Factor Binding Protein to Modify the Coagulation Cascade and Establish Host Infections https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388267/

The Influence of certain Bacteria on the Coagulation of the Blood https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2105975/

Effect of Antibiotics on Staphylococcus aureus Producing Panton-Valentine Leukocidin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855455/

Community-acquired necrotizing pneumonia due to methicillin-sensitive Staphylococcus aureus secreting Panton-Valentine leukocidin: a review of case reports https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259061/

Staphylococcus aureus, master manipulator of the human hemostatic system https://onlinelibrary.wiley.com/doi/10.1111/jth.13928

Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002307

The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus https://cmr.asm.org/content/30/4/887

POLL RESULTS

I

• give in to temptation, it may not pass my way again 16%
• find temptation unspeakably desirable. 12%
• think between two evils, I always pick the one I never tried before. 24%
• can resist anything except temptation. 8%
• generally avoid temptation unless I can't resist it. 32% Other Answers 8%
• am old now, and am seldom tempted by much of anything, or anyone.
• I always choose the larger of two weevils. -Jack Aubrey

You Got Questions? I Got Answers. Sort Of.

Nov 19, 2020

Do you know who I hate more than anyone in the world ever? The person who invented the caps lock key. On the keyboard, caps lock is next to the third most common letter, 'a'. On my Mac, I have it turned off, but at work? I can't turn caps lock off and, as passwords are starred out, I never notice I have caps lock on until I hit enter. I wonder how much of my computer time is spent correcting caps lock errors.

The patient is being treated for latent Tuberculosis. He had a distant potential exposure 50 years ago but now is asymptomatic and has a normal CXR.

He has a new diagnosis of bladder cancer, and they want to use BCG. So they sent him to me with several questions for which I have answers. Well, I have opinions, but I found little on Google or PubMed to support me.

Should he continue his latent TB therapy while getting BCG?

I thought not. If the BCG is killed off by the TB meds, I would expect it to have less effect on cancer. But I find nothing to support that idea. The cancer has the priority, so stop the latent TB therapy for now.

Will the latent TB affect the efficacy of the BCG? Interesting question. You would think a latent TB patient would have a more robust reaction to the BCG and a better response to therapy. But no one has ever looked at that either. The best you can say is that priming with the BCG vaccine may lead to a better response to intravesicular BCG.

And it may depend on the BCG strain, as they have evolved in the lab in different directions. BCG Danish and BCG Japan lead to more inflammation than BCG Russia.

Will the latent TB prevent the spread of the BCG? Curious question. BCG doesn't prevent TB all that well, so I suppose the converse is true.

We found no significant differences in terms of demographics, comorbidities, or previous diagnosis of active or latent tuberculosis infection between patients with and without systemic BCG infection.

But that is based on very small numbers. And there are case reports of TB in various organs after BCG therapy. So I suspect BCG therapy does little to prevent TB and vice versa.

But I am surprised no one has looked at the issues before.

Rationalization

Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025668/

Early Vaccination With Bacille Calmette-Guérin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial https://academic.oup.com/cid/article/71/8/1883/5611188

Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer Incidence, Risk Factors, and Outcome in a Single-Institution Series and Review of the Literature https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602419/

Note

Per the Wikipedia, in text (which I used) a is third most common letter after e and t. A is fourth in dictionaries after e,s, and i.

There are three ways to count letter frequency that result in very different charts for common letters. The first method, used in the chart below, is to count letter frequency in root words of a dictionary. The second is to include all word variants when counting, such as "abstracts", "abstracted" and "abstracting" and not just the root word of "abstract". This system results in letters like 's' appearing much more frequently, such as when counting letters from lists of the most used English words on the Internet. A final variant is to count letters based on their frequency of use in actual texts, resulting in certain letter combinations like 'th' becoming more common due to the frequent use of common words like "the", "then", "both", etc. Absolute usage frequency measures like this are used when creating keyboard layouts or letter frequencies in old fashioned printing presses.

An analysis of entries in the Concise Oxford dictionary, ignoring frequency of word use, gives an order of "EARIOTNSLCUDPMHGBFYWKVXZJQ".

POLL RESULTS

I hate

• caps lock 24%
• control-alt-delete 8%
• ~ 12%
• tab 12%
• windows key 36% Other Answers 8%
• my new Gateway thing, which has Borked my network and flabberd my printer's gast.
• Scroll Lock. The key location varies from keyboard to keyboard.

Is it a thing?

Nov 24, 2020

The question of the last week or so as I wander the hospital is, "Are you going to get the COVID 45 vaccine?

Yep.

Which one?

Probably the first one I can. But data is still preliminary.

The way I figure it, my chance of severe disease, given my age and co-morbidities, is around 5% and perhaps a 1% chance of death. That does not thrill me. I would not put a gun to my head and pull the trigger if I had a 1 in 100 chance of blowing my brains out. And I see COVID patients every day, albeit dressed to the PPE nines.

There is no way any vaccine is going to have anything close to that morbidity/mortality of COVID 45. Relative risk? Easy. Get the vaccine.

And if there are long-term complications? I'm 63. I'll be dead in the next 25 years. Long-term complications are not an issue for me. I wonder if I should get the one-year NEJM subscription instead of the two years, so I don't pay for something I may not need.

Plus, I want to see my mother again, who is 90, independent but with significant co-morbidities, before either of us dies. Given the rampant dumbassitude with which Americans approach masks, vaccines, and COVID, the vaccine is high on my to-do list.

And it will be nice to eat out and travel again. Do you realize I had to cancel my yearly trip to see the in-laws? Poor, poor, pitiful me.

The patient was admitted with a day of intractable, Vesuvius imitating, vomiting, cramps followed 24 hours into the illness by a rigor and a fever. We never did figure out the cause of the vomiting. I suspected a S. aureus toxin, since he was better in a day or so. Yes,S. aureus food poisoning doesn't cause fever. We will get to that.

I think I had S. aureus food poisoning at IDSA many years ago. Passed out from the puking. I remember waking up on the bathroom floor, really unable to move, thinking, well, housekeeping will find me. I eventually recovered without needing to frighten housekeeping. Didn't learn much at that IDSA.

S. aureus makes 25 enterotoxins! Remarkable. Enterotoxins are quite a complex subject, but I could not find an answer to the question I always wonder about with toxin-mediated disease. Is causing diarrhea, or toxic shock, or botulism or tetanus the real purpose of the toxin, or are the diseases these toxins cause a side effect, and their 'real purpose' remains unknown. I can't see how inducing TSS or 24 hours of vomiting is beneficial to the organism. Cholera toxin, I can understand. But not these.

Anyway.

Fevers result in blood cultures, both of which grew C. albicans in around 24 hours. I would not have bet on that.

Nothing in the history to suggest a risk for fungemia. An endoscopy found no tears or AVMs to blame, just some irritated gastric mucosa. Not even thrush.

Now what?

Vomiting may be a manifestation of a primary bloodstream infection. Maybe. It is not as reliable as chills.

The presence of vomiting was also addressed, but neither a univariate nor a multivariate logistic regression showed any association between vomiting and bacteremia.

My just-so story is that in less sanitary times, the primary source of infectious disease was contaminated food and water, and evolving a way to get source control, TNF/cytokine-induced vomiting and diarrhea is the result.

But his fevers occurred 24 hours into his illness. Temporally, the vomiting preceded the bloodstream infection, so I suspect the vomiting caused the fungemia. But if that is the pathophysiology, I can't find case reports. Not even in hyperemesis gravidarum. I found even fewer cases of Candidemia after severe vomiting.

So is bloodstream infection as a consequence of severe vomiting a thing? Perhaps. It is the only explanation I have.

It was hard to ignore the cultures and hard to believe them. But I ended up treating with 14 days of fluconazole.

Rationalization

Toxins (Basel). 2010 Jul; 2(7): 1751 1773. Published online 2010 Jul 5. doi: 10.3390/toxins2071751 PMCID: PMC3153270 PMID: 22069659 Food Poisoning and Staphylococcus aureus Enterotoxins https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153270/

Basis of Virulence in Enterotoxin-Mediated Staphylococcal Food Poisoning https://www.frontiersin.org/articles/10.3389/fmicb.2018.00436/full

POLL RESULTS

I plan on

• getting the first covid 45 vaccine asap 56%
• waiting a bit to see which one is most effective/least toxic 24%
• avoiding the vaccine as we have turned the corner on that hoax 2%
• seeing if maintaining a high blood alcohol level at the local bar will take care of the covid 45 2%
• avoiding the vaccine as I am allergic to tracking nanobots 7% Other Answers 7%
• rely on social hermit status
• getting the first covid-19 vaccine asap
• Let the Britains vaccinate their +80 first and see what happens.

Late Sepsis or Something Else?

Nov 30, 2020

The patient has widely metastatic cancer and comes in with jaundice and an altered mental status. The temperature was 100.8, and blood cultures were drawn. Twenty-four hours later, both sets grow a gram-positive rod, and one grows a gram-negative rod. Vancomycin and Ceftriaxone were started, and the next day they are identified as Listeria and* Shewanella**algae*. I assume you know which one is purple and which one is red.

They called me, and I changed the vancomycin to ampicillin. History yields no important dietary habits that would lead to Listeria, but he is elderly. One of the concepts that guide my understanding of the universe is that everything we eat is covered with a layer of stool; it is just a matter of how thick and with what pathogen. Exposure to Listeria is, therefore, to be expected. There were no signs or symptoms of meningoencephalitis, and LP was refused by the patient.

The Shewanella? It is found in

marine or aquatic exposure, especially during relatively warmer months.

And there are a hodgepodge of reported infections. He had been near no odd water sources, and it has been cold recently. And he was not training to be a Navy Seal. So, no clue where the Shewanella came from.

For 24 hours, he did fine, then abruptly decompensated and expired. But it was a peculiar decompensation: refractory hypotension, marked hypothermia, the sodium went down, and the potassium went up. It seemed a bit late to be due to endotoxin-mediated sepsis.

It looked like acute adrenal insufficiency. I have seen a few cases over the years. Hydrocortisone was given to no avail, and we never had the labs to confirm the diagnosis.

The CT did not show mets to the adrenal, so that may not be the reason. With extensive liver involvement by the cancer, perhaps there was decreased substrate:

cholesterol which comes from liver via high density lipoprotein (HDL) particles is taken up by adrenal gland which expresses scavenger receptor type B1 (SR-B1) for HDL; (ii) cortisol is synthesized in the adrenal cortex starting with cholesterol as substrate for cholesterol side-chain cleavage enzyme.

But could it be sort of a Waterhouse--Friderichsen syndrome, but due to infection instead of infection?

There are no cases in humans of either Listeria or Shewanella causing acute adrenal insufficiency, but in animals, there is

Focal necrosis of the liver with infiltration of mononuclear cells is a typical histopathological finding in septicemic animals, sometimes also affecting the spleen, lungs, and other organs such as the tonsils, intestinal tract or adrenal glands

and more interestingly

The infection of mice with Listeria led, in case of the development of an acute generalized form of the disease, to the sharp decrease of the content of ascorbic acid and to the nearly complete delipidization of the glomerular zone of the adrenal cortex, which was indicative of the development of relative adrenal insufficiency. The most pronounced histomorphological and histochemical changes occurred simultaneously with the maximum accumulation of Listeria in the adrenal glands. The administration of hydrocortisone at the period of the development of acute infection produced a temporary decrease in the manifestations of toxicosis. The maximum protective effect was achieved by combined glucocorticoid and antibiotic therapy.

So maybe a perfect storm. We will never know. But an interesting to think about and does beg the question as to what is the effect of disseminated Listeria on the adrenals.

Rationalization

Shewanella algae - A Novel Organism Causing Bacteremia: A Rare Case and Literature Review https://pubmed.ncbi.nlm.nih.gov/33133842/

Shewanella algae Infections in United States Naval Special Warfare Trainees https://pubmed.ncbi.nlm.nih.gov/31696143/

Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240761/

Animal models of listeriosis: a comparative review of the current state of the art and lessons learned https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384455/#B23

[The significance of corticosteroid insufficiency in the mechanisms of toxicosis in experimental listeriosis] https://pubmed.ncbi.nlm.nih.gov/3218428/

Unexpected Yeast

Dec 3, 2020

The patient has upper GI surgery involving the stomach and the esophagus. He does well post-op, except he develops a leak of the esophageal-gastric junction, which leads to a pleural effusion. It is tapped and not cultured but treated with Augmentin.

Don't get me started.

Several weeks later, he returns with a recurrence, a chest tube is placed, and when the cultures grow *Saccharomyces**cerevisiae* aka bakers or brewers yeast, they call me.

That was not what I would have expected. I have seen a variety of Saccharomyces cerevisiae infections, but most have had a yeast exposure - baking, brewing, and pruno - as a risk.

In this case? Nothing.

So I went looking. To my surprise, Saccharomyces cerevisiae is part of the human microbiome.

However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers...

and

The rate of Saccharomyces carriage varies according to the populations investigated. A study from the 1940s reported that the respiratory tract of 7% of patients with chronic pulmonary disease was colonized with Saccharomyces organisms . Occasionally, S. cerevisiae can be isolated from the vaginal flora (0.9%-5.8% of women), and S. cerevisiae is considered to be responsible for symptoms mimicking Candida vaginitis in 0.4% of cases. A more recent study involving patients with hematologic disease reported isolation of S. cerevisiae from throat, stool, urine, and perineum samples in 16%, 23%, 10%, and 20% of the patients, respectively. It is not known whether S. cerevisiae is a persistent commensal of the digestive tract or whether it is only transiently present after food ingestion.

I am always amazed at the things I do not know. So I do not have to blame Red Star or Fleishmans as the source of the yeast. It was likely the patients own Saccharomyces.

There are maybe three cases Saccharomyces empyema in the medical literature, with one

S. cerevisiae after oesophageal perforation, soon after ingestion of beer.

The leak was treated with an esophageal stent. A low pathogenicity organism, a chest tube, and an azole were curative.

Rationalization

The gut mycobiome of the Human Microbiome Project healthy cohort\ https://microbiomejournal.biomedcentral.com/track/pdf/10.1186/s40168-017-0373-4.pdf

Invasive Saccharomyces Infection: A Comprehensive Review https://academic.oup.com/cid/article/41/11/1559/356155

Boerhaave's syndrome complicated by a Saccharomyces cerevisiae pleural empyema. Case report and review of the literature https://pubmed.ncbi.nlm.nih.gov/29103370/

An Evening Drink http://boards.medscape.com/forums/?128@@.2a06bdbb!comment=1

Baking and Brewing http://boards.medscape.com/forums/?128@@.2a80118b!comment=1

It Wasn't. Probably

Dec 7, 2020

I was called to see a rash. Well, rashes. I'm not good at rashes, but they call me anyway, and mostly I tell them what it isn't.

She had:

Multiple itchy nodules that looked kind of warty.

Small, superficial ulcers on the arms and chest. It looked like it was from scratching. She said it wasn't.

Increased darkening of the skin. She is African American and noted that her skin, especially the arms, were getting blacker. This is not my color, she insisted.

The legs were hyperkeratotic like chronic stasis changes, with some small ulcers and painful when in the dependent position. It kind of looked like pahoehoe lava. Really.

I know. The above descriptions are sorely lacking.

Talking with her, she had no past medical history of note, except she had been homeless for six months, no risks or exposures for anything.

All the routine labs were negative.

I didn't recognize any of the skin conditions. So, I said, pending dermatology consultation, this is nothing I recognize. No scabies, no adrenal disease, no topical dermatitis, no HIV, no nothing.

My rule? When I can't recognize a disease, then it is either syphilis or some weird cancer.

And the FTA was positive.

But the RPR? Negative.

And the patient? Shocked at a diagnosis of syphilis. No recent risks, no prior diagnosis or treatment.

I searched the web, looking for a syphilitic rash that was similar and maybe, maybe not. Some version of lues maligna?

Lues maligna was first described in the 1800s and represents a severe form of secondary syphilis. The lesions of lues maligna have an ulceronodular appearance unlike the classic mucocutaneous eruption of secondary syphilis. In addition, lues maligna typically involves the trunk and extremities but rarely the scalp. The rash bears resemblance to that seen in yaws and the gummatous lesions of tertiary syphilis with multiple, well circumscribed, ulcerations that have a characteristically crusted borders and minimal surrounding erythema, although the lesions can also present as pustules.

Not really. But kind of. Maybe. But because it would be a cool diagnosis, I spent a lot of time in the secondary syphilis rash literature. Interesting and icky stuff.

Maybe the negative RPR was due to the prozone effect.

Prozone phenomenon is a false negative response resulting from high antibody titer which interferes with formation of antigen-antibody lattice, necessary to visualize a positive flocculation test. We present a case of secondary syphilis who presented to us with features of contact irritant dermatitis.

Although the prozone effect is rare:

The overall rate of the prozone phenomenon was 2 out of 3222 samples (0.06%).

Another study found a rate of 0.83%.

So we gave her a shot of benzathine, and, as it was a Friday afternoon, she was discharged with follow-up with me and dermatology.

I asked the lab to titer out her serum. They got to 1:4000 and gave up. No positive RPR. No prozone effect. It is likely not syphilis.

Saw her back a week later and her legs were much improved, but that could have been due to improved care at the wound clinic. So no diagnosis, at least an ID diagnosis. We will see if dermatology finds the answer on a biopsy.

Never went to derm, so no diagnosis in the end.

Rationalization

Indian J Sex Transm Dis AIDS. 2011 Jan-Jun; 32(1): 47 49. doi: 10.4103/2589-0557.81256 Prozone phenomenon in secondary syphilis https://pubmed.ncbi.nlm.nih.gov/21799578/

Clin Infect Dis. 2014 Aug 1;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 https://pubmed.ncbi.nlm.nih.gov/24803377/

Sex Health. 2012 Nov;9(5):488-90. doi: 10.1071/SH11156. Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology - an infrequent but important laboratory phenomenon https://pubmed.ncbi.nlm.nih.gov/22958508/

Lues Maligna Open Forum Infect Dis. 2017 Summer; 4(3): ofx139. Published online 2017 Aug 3. doi: 10.1093/ofid/ofx139 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300306/

POLL RESULTS

When I don't recognize a disease it's likely

• syphilis 42%
• hiv 0%
• a weird cancer 25%
• an illusion 17%
• never happens to me 4% Other Answers 13%
• atypical presentation of common condition
• "just" gas. Or pancreatic cancer. Choice is yours.
• tuberculosis

Another Violation of Fundamental Laws

Dec 9, 2020

The patient, with no prior medical problems, has been chopping wood on and off for the last few months. Tweaked his back a couple of times, but each time it recovered in a day.

Then a month ago, the back snapped, and the pain was severe with lots of back and abdominal wall spasmsno other symptoms.

He went to the ER, where he had an MRI. T10 is sclerotic. I later looked at it, and there were no changes to suggest infection. The rest of the labs were normal.

He was sent home with pain medication, and the pain progressed in the back, and he developed a fever and abdominal pain. A CT of the abdomen was normal, but the CT picked up a new T10 compression fracture.

The next day, the blood cultures and the urine cultures were growing MRSA, and they called me. Nothing of note on the history except a lot of minor trauma to the skin, part and parcel of chopping wood.

Here is how I put it together: he had minor trauma to T10 seeded from the cutaneous injury. It progressed to destroy T10 with bacteremia and seeding the bladder. The CT looked like an infection of the spine, and the abdominal pain was due to T10 nerve root irritation. It would not be the first time I have seen abdominal pain was nerve root in origin, but I guess it's rare.

There are few case reports describing abdominal pain, resulting from a thoracic disc prolapse. These indicate that there is no consistent mode of presentation of the pain in its nature, site or duration. In the case we have described, the site (left iliac fossa) and nature of the pain (intermittent or colicky) has, to our knowledge, not been previously reported.

The CT looked just like an infection. But. The MRI suggests the infection directly seeded the bone. And the law, one that is inviolate, is that infection goes to disc and then to both adjacent vertebral bodies. Tumor goes to bone and spares the disc space. He broke the law.

It is rare to get an infection in the middle of the bone. I suppose it could be called a Brodie's abscess, i.e., an intraosseous abscess of the vertebral body, although Brodies are usually subacute.

The first case was treated rather aggressively:

It's first description in the medical literature was in 1832 by sir Benjamin Brodie during a lecture held for the Medical and Surgical Society. The first case he described, a 24-year old male, had suffered half his life with bouts of severe pain originating from a bony swelling above the right ankle. Since no other treatment was successful they decided to amputate the affected limb. Examination of the amputated specimen showed a walnut sized collection of pus.

Can't remove the spine, an intervention usually reserved for US Senators and Congressmen.

There are maybe four reported vertebral Brodies I can find. And there are cases of vertebral osteomyelitis breaking the law by avoiding the disc and paraspinal structures. In fact, when researching the issue, one of the first hits on Google was my blog entry from a year ago. This is an increasingly common phenomenon as I age: I don't remember the odd cases, but Medscape has saved them for me.

Now a long course of antibiotics and, I hope, a cure.

Rationalization

Thoracic Disc Prolapse Presenting with Abdominal Pain: Case Report and Review of the Literature https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758438/

Brodie's Abscess: A Systematic Review of Reported Cases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367194/

Vertebral osteomyelitis without disc involvement https://www.sciencedirect.com/science/article/abs/pii/S0009926004001333

Unusual Manifestations of Vertebral Osteomyelitis: Intraosseous Lesions Mimicking Metastases http://www.ajnr.org/content/29/6/1104

Pyogenic vertebral osteomyelitis presenting as single spinal compression fracture: a case report and review of the literature https://pubmed.ncbi.nlm.nih.gov/11093326/

Two Rules, No Exceptions http://boards.medscape.com/forums/?128@@.2a83dc6f!comment=1

POLL RESULTS

To remember old cases I

• keep a journal 0%
• write a blog 11%
• tattoo them on my skin 6%
• leave Post-It notes everywhere 39%
• consign them to the dustbin of history 39% Other Answers 6%
• just think of times when other techs have screwed up royally and I had to fix things or we would end up in court or the morgue or both.

Turning European

Probably Maybe

Dec 17, 2020

The patient is a young male with two months of fevers, night sweats, malaise, and a 10 lb weight loss. During this time, he also developed some chest pain that led to a CT that revealed lymphadenopathy that led to a lymph node biopsy that led to an ID consultation.

By the time he made it to clinic, he was on the mend. Getting better, not the video clinic visit. The constitutional symptoms were gone, and his weight had returned.

But what to make of the biopsy, which showed necrotizing granulomas? Special stains were negative.

Exposure history was unremarkable. A dog and, seven months ago, a cat bite from a since expired cat.

Examination and routine labs are unrevealing; the referring doc had sent fungal studies and a Quantiferon, all of which were negative.

Necrotizing granuloma has a broad differential:

most commonly infection, Wegeners, aspiration pneumonia and less commonly rheumatoid nodule, necrotizing sarcoid granulomatosis (NSG), infarct and lymphomatoid granulomatosis...

Although only the infectious causes are of interest.

I bet on Cat Scratch disease, as cats were the only exposure, albeit remote. But the studies were negative. So I sent off molecular testing as well, a Karius test. Nothing.

So now I am betting on Kicuchis. Why not?

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare and self-limited syndrome characterized by tender cervical lymphadenopathy,

and he fits the clinical pattern. Mostly:

The most common clinical presentation is fever and cervical lymphadenopathy in a previously healthy young female. Rash, arthritis, fatigue and hepatosplenomegaly are other, less frequent, manifestations although there are case reports in the literature of more serious presentations such as meningitis, polymyositis and acute cerebellar syndromes. Laboratory studies in people with Kikuchi disease are fairly non-specific. The most common finding is leukopenia, followed by atypical lymphocytes; however, the majority of patients have a normal Complete Blood Cell count. Erythrocyte Sedimentation Rate also tends to be elevated in most patient and there may also be abnormalities in liver enzymes and an elevated LDH.

The disease is likely an exuberant immune response to an infection, although whether it is a specific infection or a reaction to a variety of infections is unknown. There is also an association with autoimmune diseases that this patient doesn't have.

This is not the first time I have credited necrotizing granuloma to Kikuchi's. And while the molecular testing was negative, it was sent two months after symptom onset, so not sure it excludes infectious etiologies.

Rationalization

Necrotizing granulomatous inflammation: what does it mean if your special stains are negative? https://www.nature.com/articles/modpathol2011155

Kikuchi Disease: The Great Masquerador - A Case Report and Review of the Literature https://medical-case-reports.imedpub.com/kikuchi-disease-the-great-masquerador-a-case-report-and-review-of-the-literature.php?aid=22921

Odd Nodes http://boards.medscape.com/forums?128@@.2a80d78d!comment=1

Infections Take a Holiday

Dec 22, 2020

My goal for 2020 had been simple: avoid dying of COVID 45. Today I got my vaccine, so it looks like I made it. Although my son is worried I will be like the cop in the movies who has two weeks until retirement: you know he's a goner in the first act.

It is nice the vaccine is here, and I will no longer have to worry about catching or giving COVID 45 to others, but I have little enthusiasm that it represents the beginning of the end of COVID. If we can't get people to mask and distance to prevent spread, no way are those folks going to get a vaccine. I expect the pandemic to go from a roiling boil to a modest simmer, but it will not be going away any time soon. And if we can't get people to mask and distance, simple, painless interventions, no way are we going to be able to accomplish the needed interventions to combat climate change.

We are so doomed.

For the last couple of weeks, I have wondered where all the infections have gone. Both times the COVID curve has pointed up, my usual practice vanished. Where were the IVDAs with bacteremia? The FUOs? The abscesses? All gone.

Then when the curve peaks and starts down, as it has in Oregon, the non-COVID infections come roaring back. From where? I don't know. I wonder if the coming post-Christmas COVID surge will see the same pattern?

The patient feels poorly and has relatively severe axillary pain. She goes to bed and, upon awakening, finds the left side of the chest red, hot, tender, and swollen. She is admitted for cellulitis, and as the erythroderma spreads, they call me.

I wasn't too worried; it takes time for antibiotics to kick in, so I recommended staying the course as well as the usual stop the vancomycin. It should all be Group A Streptococcus. And she slowly got better.

But I want to point out the axillary pain. Medicine is like Bach, variations on a theme. I have discussed what I like to modestly call Crislip's sign before: inguinal pain that precedes the classic rubor, dolor, calor, and tumor of cellulitis. My hypothesis has been it is due to Streptococcal lymphadenitis. I have never seen this mentioned anywhere but this blog, but I see it once or twice a year.

This is the first report of Crislip's sign in an axilla, occurring before the symptomatic cellulitis. Further confirmation that this is a real phenomenon and widely applicable. Now I just need a facial cellulitis with preceding posterior auricular pain.

Now I have real Science to lend respectability to my hypothesis:

Long recognised as a barrier or as a conduit for infectious pathogens travelling within leukocytes, research has focussed on the interaction of the lymphatic system with intracellular microbes; from plague and tuberculosis, to viruses and parasites. The potential for extracellular bacteria to access this system has been largely ignored, as an accidental consequence of normal interstitial fluid transport. Group A streptococcus, a virulent human pathogen that is known for its capacity to disseminate systemically, can rapidly access the lymphatic system and local lymph nodes via a hitherto unrecognised but specific interaction between its hyaluronan capsule, and the lymphatic endothelial receptor LYVE-1.

and

In conclusion, we describe a novel interaction between GAS capsular HA and the lymphatic endothelial receptor LYVE-1 that provides an important conduit by which encapsulated streptococci can disseminate into the lymphatic vasculature. To our knowledge this represents the first identification of a molecular mechanism for entry into the lymphatic system by an extracellular pathogen. Moreover, our findings provide a molecular explanation for the clinical observation that local lymphatic drainage plays a major role in limiting immediate systemic spread by GAS.

Group A Streptococci have an affinity for lymph nodes. It looks like there is a biological explanation for Crislip's sign. Medical immortality is just around the corner.

Rationalization

Nothing to see Here, Keep Moving http://boards.medscape.com/forums?128@@.29f6358b!comment=1

Just So http://boards.medscape.com/forums?128@@.2a09b42d!comment=1

Crislip's Sign http://boards.medscape.com/forums/?128@@.2a32c105!comment=1

Streptococcal lymphatic metastasis: Bacterial close encounters of the fourth kind https://www.ijidonline.com/article/S1201-9712(16)30005-4/fulltext

Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005137

Streptococcus pyogenes interaction with the lymphatic hyaluronan receptor LYVE-1 as a mechanism for lymphatic dissemination and disease progression https://gtr.ukri.org/projects?ref=MR%2FL008610%2F1

POLL RESULTS

The COVID 45 vaccine

• changes nothing 2%
• changes everything 19%
• will take the edge of the pandemic 47%
• has messenger RNA. Just who is it messaging? 14%
• is rearranging the deck chairs on Titanic Earth 19%

50,000 Speculation

Dec 24, 2020

Still weirdly slow, the COVID draught combined with the usual pre-Christmas slowdown. Not that I am complaining. When I started in practice in the summer of 1990, I worried about the occasional slow times. Do they not trust me? Why aren't they calling me? Where are the infections?

Now? What, me worry? Although I am always glad to see a consult, and I am always surprised when someone apologies for consulting me. It is how I pay the bills, and it is my raison d'etre.

But little to write about, so I will speculate instead.

The patient is admitted with sepsis and hypotension after being found down after heroin use. In the first 24 hours, he has two CBC's, both 50,000.

Of note, he has been in and out of the hospital since June with multilevel MRSA spinal osteomyelitis, leaving AMA. At best, he keeps getting half a course of vancomycin at Outside Hospital.

Evaluation with pan CT does not show any new infections or collections of pus that need draining, although the spine is progressing. All the cultures are negative.

Within 24 hours, when they call me, the WBC is 21K, the patient is back to baseline, and has no complaints except his back.

So why the leukemoid reaction? I can't find a reason in the evaluation to date, and there is no way 24 hours of vancomycin will lead to that kind of improvement with MRSA osteomyelitis.

So I ask, among other things, how the patient uses: he mixes the heroin with tap water, heats it up, filters through cotton balls, and injects.

Cotton fever? My bet. What is cotton fever?

Cotton fever is a diagnosis of exclusion and is characterized by acute onset of fever and leukocytosis immediately following intravenous drug injection when filtering through cotton. Symptoms begin 15--30 minutes following injection, and are often accompanied by shortness of breath, chills, headache, myalgia, abdominal pain, nausea, vomiting, and tachycardia. Although cotton fever is self-limited and normally lasts 6 to 12 hours, it can continue for up to 24 to 48 hours.

I suspect it isn't the cotton that is causing this kind of SIRS response.

It doesn't take much endotoxin to get a leukocytosis or fever; a few nanograms is all. And he is behaving clinically as if he had a transient insult that led to his clinical course. And cotton balls may be full of endotoxin.

Finally, the endotoxin theory suggests that cotton fever may result from the release of endotoxins from Gram negative bacilli such as Enterobacter agglomerans, which has been shown to regularly colonize cotton. Further supporting this endotoxin theory, a case of cotton fever was described in conjunction with E. agglomerans bacteremia.

As well as my case referenced below. So I am calling it a leukemoid reaction from the mischaracterized cotton fever.

No entries next week. I wish you all a generic nondenominational seasonal greeting and a happy new year. See you in 2021.

Rationalization

J Gen Intern Med. 2016 Apr; 31(4): 442--444. Published online 2015 Jun

24. doi: 10.1007/s11606-015-3424-1 Cotton Fever: Does the Patient Know Best? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803705/

I Don't Cotton to That http://boards.medscape.com/forums/?128@@.2a064487!comment=1

Schooled

Jan 18, 2021

No, I am still around. Week before last, the blog was having issues and would not let me post. I didn't take the hint, I'm back. Then a week off, which I really hope occurs more often as I slide into senescence. As much as I like ID, I do like not working. As I have mentioned before, no one in the history of the world has ever said at the end of life, "Doc, I regret not have spent more time at work."

The patient, from Africa years ago, has an isolated cervical lymph node that has been slowly growing. He has no other symptoms. Resection has granulomas and eventually grows MTb.

CXR is clear.

County Tb takes care of all these patients with directly observed therapy, and they require three sputa. Although I always say three sputums. Sputa may be the correct plural, but I have never heard it used.

Sure. They always want three SPUTA. It seems a waste of money as the SPUTA is always negative. Except this time. While smear-negative, the sputum grows MTb.

Maybe not such a waste of money after all.

With no cough and a clear CXR, he isn't all that infectious. Tb is one of those diseases I would say my knowledge base is reasonable but not exhaustive. I see one or two cases a year, and Tb has what seems to be almost infinite clinical variations.

Just how often does sputum grow MTb in extrapulmonary disease and a clear CXR?

However, the rate of normal CXR among EPTB patients with positive sputum culture results was relatively high. Therefore, respiratory specimen cultures should be obtained in TB suspects with a normal CXR to identify potentially infectious cases of TB.

Or 4/17, 24%. I was surprised. That is a lot.

And another study found 5% of HIV-negative with culture-positive TB had a negative CXR. 9% in HIV positive.

Part of the problem is the CXR is not that reliable a test.

CXR has been used for over a century to diagnose pulmonary TB; however, it is limited by modest specificity with a high interobserver variability in radiological reports

Although I looked at the CXR, and despite a tendency to over-read everything, I saw no pathology.

A CT may be the real screening test if the CXR is negative:

CT scan in those with normal radiography increased the detection of cavities.

and

Subjects with normal or equivocal CXR may have findings indicative of active TB on chest CT.

It depends in part on what the population being studied is. I suppose in the future, I would consider a chest CT in an extrapulmonary TB with a negative CXR, mostly for transmission worries. But

Otherwise this diagnostic tool should be carefully considered, taking into account its risk (radiation) and cost.

I'm sure Tb will school me again.

Rationalization

J Family Community Med. 2012 May-Aug; 19(2): 88--92. doi: 10.4103/2230-8229.98287 Predictors of pulmonary involvement in patients with extrapulmonary tuberculosis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410185/

Int J Tuberc Lung Dis. 2008 Apr;12(4):397-403. Normal chest radiography in pulmonary tuberculosis: implications for obtaining respiratory specimen cultures https://pubmed.ncbi.nlm.nih.gov/18371265/

Diagnostic Accuracy of Chest Radiography for the Diagnosis of Tuberculosis (TB) and Its Role in the Detection of Latent TB Infection: a Systematic Review https://doi.org/10.3899/jrheum.140100

Infect Drug Resist. 2018 Jan 3;11:37-43. doi: 10.2147/IDR.S151844. eCollection 2018. Performance of computed tomography versus chest radiography in patients with pulmonary tuberculosis with and without diabetes at a tertiary hospital in Riyadh, Saudi Arabia https://pubmed.ncbi.nlm.nih.gov/29379307/

Pattern Recognition

Jan 20, 2021

The patient is two weeks into their COVID and remains on a ventilator. She had a course of remdesivir and dexamethasone and was stable. The then fevers began. Each day a little higher and never returning to normal. 38, 39, 40, 41. Every day more febrile.

I did the four-star workup for infection and found nothing. So I was betting on drug fever, although the only potential drug was the ketamine.

Not that there are a lot of cases of ketamine-induced drug fever. Like almost nothing.

So we stopped the ketamine.

And the fevers did not remit.

Medicine is all about recognizing patterns, but it is hard to recognize a disease you have never seen. I like to mention how early in my practice, I missed Stills several times in a single year because I did not recognize the pattern. I do now.

The patient had a low WBC. From the COVID.

A high ferritin. 900. From COVID.

A pustular rash on the chest. That I didn't recognize.

A mildly enlarged spleen. Not certain why.

An elevated CRP. 210. From COVID.

So what was it?

The pattern was recognized by ICU attending. What about hemophagocytic lymphohistiocytosis, he asked? I just shrugged. Never saw a case, I said. Vaguely remember HLH from a case I saw as a fellow. I also vaguely remembered a couple of case reports of HLH following COVID. So I looked it up; she did meet the diagnostic criteria. We clinched the diagnosis as the soluble CD25 receptor was sky-high.

We never did a biopsy to demonstrate haemophagocytosis in the bone marrow, spleen or lymph nodes.

But there are numerous cases of COVID and HLH, and one article notes that the COVID inflammatory state resembles HLH

The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring.

and

HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment.

Although a lot of the serologic findings of COVID do not necessarily mean HLH:

Though many patients with COVID-19 present with hyperferritinemia, elevated ferritin levels are not accurate predictors of outcomes and do not appear to be indicative of hemophagocytic lymphohistiocytosis.

There are a remarkable number of cases and reviews on this issue, given the disease is only a year old. Fever resolved instantly with a dose of steroids, although she eventually succumbed to progressive pulmonary failure.

And, like all cases whose diagnosis I missed, I will be hyper-vigilant about HLH in the future. As "there's an old saying in Tennessee --- I know it's in Texas, probably in Tennessee --- that says, fool me once, shame on --- shame on you. Fool me --- you can't get fooled again."

Wise words for all.

Rationalization

Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases? https://pubmed.ncbi.nlm.nih.gov/32664932/

Ferritin levels in patients with COVID-19: A poor predictor of mortality and hemophagocytic lymphohistiocytosis https://pubmed.ncbi.nlm.nih.gov/32790918/

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic https://pubmed.ncbi.nlm.nih.gov/32588191/

No one knows what it's like...behind blue eyes

Jan 26, 2021

Six months ago, the patient presented with fever and liver pain. Work-up eventually found bleeding into the liver due to ruptured aneurysms. They were coiled.

Two weeks later, he represented with RUQ pain and fever. A liver abscess was found, drained, grew E. coli, and he received a four weeks course of ceftriaxone and was all better.

Six months later, he returns with right upper quadrant pain and fevers. CT shows an abscess in the same location. This time they call me. New or relapse? It seems a long time for an E. coli to fester under the radar, but there is a titanium coil in there that could serve as a nice nidus for recurrence.

Coil infections are uncommon:

Seven case reports of patients who experienced infection related to coils used for embolization of arteries were discovered. Arteries embolized with coils in these patients were intracranial, intraabdominal, and intrathoracic, respectively, in four, two, and one case. Abscess formation in the area of coil placement (n = 6; 85.7%) was the most common infectious complication directly related to endovascular coil embolization. Staphylococcus aureus was the predominant isolated pathogen (n = 3; 42.9%). Other isolated pathogens included Salmonella species type D (n = 1; 14.3%), S. epidermidis (n = 1; 14.3%), Escherichia coli (n = 1; 14.3%), and Bacteroides fragilis (n = 1; 14.3%). Surgical procedures were performed in four of the seven patients described (57.1%), and three patients were treated with only the administration of antimicrobial agents.

This time it grew Enterococcus. So we treated that, and he got all better. But what to do long term. If it were a prosthetic joint or relapse, I would suggest chronic suppression. But the problem here is probably the coil is continuously washed by bowel flora.

The liver has a strategically important position in the human body, with a dual blood supply. The first supply, the portal vein, collects all blood from the intestine and drains it into the liver. The liver is therefore the first organ to encounter bacterial products and viable bacteria in cases of intestinal barrier dysfunction.

So would prophylaxis/suppression even work? Seems unlikely.

And the other question? Why does this elderly male have liver aneurysms? On exam, he has blue sclera. Man, I love the Googles:

A patient with Ehlers-Danlos syndrome type IV had a celiac artery aneurysm. There are only nine previously published cases of visceral artery aneurysms in this condition...Patients are susceptible to both aneurysm formation and spontaneous rupture of nonaneurysmal vessels resulting from extreme vessel fragility.

The patient was not particularly hyper-mobile but more flexible than me and did have boutonniere fingers. And as the review noted

The diagnosis of EDS type IV is difficult to make on clinical examination because it is characterized by its subtle clinical manifestations. Joint hypermobility is limited to the fingers, and a lack of skin hyperelasticity is typical.

But it would explain both the aneurysms and the blue sclera. I am always looking at eyes, and now and then seeing blue sclera and diagnosing EDS. Even if I cannot confirm it.

Rationalization

J Vasc Interv Radiol. 2007 Jun;18(6):697-701. doi: 10.1016/j.jvir.2007.04.015. Infections related to coils used for embolization of arteries: review of the published evidence https://pubmed.ncbi.nlm.nih.gov/17538130/

Fast-Track Clearance of Bacteria from the Liver https://www.sciencedirect.com/science/article/pii/S1931312816302670

Visceral aneurysms in Ehlers-Danlos syndrome: Case report and review of the literature https://www.sciencedirect.com/science/article/pii/S0741521400901162

Uncertain Etiology

Big Rat Hole

Feb 2, 2021

The patient has had nine months of dysuria and increased frequency. He was mostly living with it, thinking it was the usual after-effects of the BCG therapy, which was last received nine months ago.

Finally, complaining to the urologist, a urine culture grew BCG. The patient was sent to me.

This is not the first BCG UTI I have seen in my long and storied career. A few cystitis cases, the occasional prostatitis, a miliary case in a myelodysplastic patient, and one patient who had progressively severe hypersensitivity reaction with each dose.

BCG cystitis is common, occurring in 35%, although only about 1% get a chronic infection. It is treated like TB, with good results.

I have always wondered just how someone discovered that BCG was effective for bladder cancer. It seems, well, odd.

BCG has a curious origin, part of the investigations looking for a Tb vaccine. It was isolated

...after being grown in 231 subcultures in a medium of potatoes cooked and stored in ox bile, the strain of M Bovis was innocuous and became known as BCG.

Or as the original paper notes

This gave us the idea. That it might be easier to emulsify bacilli grown on potatoes, cooked in ox-bile and kept in hour-glass tubes containing sterile pure 5% glycerinated bile, the potatoes being dipped at one end in this extremely alkaline liquid, rich in lipids.

Of course. And they used a strain donated by Dr. Nocard, of Nocardia fame. That's kind of cool.

But why 231 subcultures? It turns out that after

230th passage on bile medium and no more modifications of its characteristics took place. Intraperitoneal injection of as much as 10 mg. BCG in guinea-pigs was followed by the formation of nodules in the epiploon, persisting several weeks without doing any damage to the animal, and finally vanishing by resorption without leaving a trace, so that when the animal was killed 5 or 6 months after the injection, it was impossible to discover the smallest lesion, even-under the microscope. It seemed that we had obtained a real vaccine, of hereditarily fixed attenuation, like Pasteur's anthrax vaccines; indeed, all our efforts to restore its virulence by passage in animals or by mixed inoculations of BOG and tuberculin or other irritating substances, were unsuccessful.

So 213 it was. But why tumor therapy?

The antitumor effect of tuberculosis was suspected as early as 1929 when the results of an autopsy study indicated a lower frequency of cancer in patients with tuberculosis and a higher incidence of active or healed tuberculosis among cancer survivors.

Probably due to TNF and part of the old literature on treating cancer with infection. Then

In 1936, Holmgren published his anecdotal experience using intravenous, subcutaneous, intraperitoneal, and intralesional BCG to treat patients with cancer.

Quite the report. Dr. Holgren noted

I have considered it to be justifiable to test the intravenous injection of BCG, since a now very great experience has shown definitely that BCG is perfectly avirulent for man...

Perfectly avirulent? Not so much.

And the rest of the 1936 article is behind a paywall. Crap, I hate that. So I have no idea how the 180 patients did with the iv BCG injections.

By the 1960s, the BCG vaccination had once again become commonplace in parts of the world, leading to the observation that there was a decreased incidence of acute lymphocytic leukemia among vaccinated children. With restored interest in the use of BCG as an immunotherapy for cancer, researchers demonstrated the regression of cutaneous melanoma after intradermal injection of BCG and the regression of metastatic melanoma in the bladder after intravesical administration of the organism. Finally, in 1976, Morales et al published the groundbreaking results of the first successful clinical trial of superficial bladder cancer treated with intravesical BCG. Although BCG therapy has been evaluated as a possible treatment for many cancers throughout the years, it has become the most effective therapy, and thus the standard of care, for NMIBC only.

Quite the history.

There are several strains of BCG, and they vary in immunogenicity.

This natural experiment is noteworthy as these different BCG strains differ in a number of in vitro properties. BCG Russia, and other strains obtained from the Pasteur Institute before 1931 ("early" strains), have an ancestral profile, which includes the secretion of the highly antigenic proteins MPT64, MPT70, and MPT83. However, BCG Danish and other strains obtained after this date ("late" strains) have mutations in their genome that have disabled or deleted the respective proteins.

In the US, there are two strains used for bladder cancer,

The Tice strain, which is a substrain of the original Pasteur product, is manufactured by Organon Pharmaceuticals. The TheraCys strain is made by Aventis/Pasteur. These products, in addition to the Tokyo 172 substrain and the Danish substrain, are available in countries other than the United States.

Are they equally effective for tumor treatment? It appears so.

It would also appear that the more immunogenic strains, like the US strains, are also more virulent in animal models with

a general trend whereby BCG strains showing higher virulence in SCID mice induced better protection against a Mycobacterium tuberculosis challenge in BALB/c mice3 relative to less virulent BCG strains.

So I would expect the prolonged cystitis would be of benefit in treating the bladder cancer.

I never tire of these rat holes.

Rationalization

Complications of Intravesical BCG Immunotherapy for Bladder Cancer https://pubs.rsna.org/doi/full/10.1148/rg.2019180014

Res Rep Urol. 2015; 7: 157--163. Published online 2015 Oct 23. doi: 10.2147/RRU.S63448 Managing the adverse events of intravesical bacillus Calmette--Guérin therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630183/

BACILLUS CALMETTE‐GUERIN (BCG) IMMUNOTHERAPY FOR BLADDER CANCER: REVIEW OF COMPLICATIONS AND THEIR TREATMENT https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1445-2197.1998.tb04768.x

Preventive Vaccination Against Tuberculosis with BCG. By PROFESSOR A. CALMETTE. https://journals.sagepub.com/doi/pdf/10.1177/003591573102401109

Employment of B. C. G., especially in Intravenous Injection https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0954-6820.1936.tb15958.x

Bacille Calmette-Guérin: One Hundred Years, One Hundred Questions DOI: 10.1093/cid/ciz1083

Early Vaccination With Bacille Calmette-Guérin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial DOI: 10.1093/cid/ciz1080

Which Bacillus Calmette-Guérin (BCG) strains are used as immunotherapy for bladder cancer? https://www.medscape.com/answers/1950803-195363/which-bacillus-calmette-gurin-bcg-strains-are-used-as-immunotherapy-for-bladder-cancer

The BCG Strain Pool: Diversity Matters https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)30325-2

I Like A Neat Package

Feb 3, 2021

I like everything tied into a nice bundle. One of my many biases is I am an Occams kind of guy. I want Non sunt multiplicanda entia sine necessitate on my tombstone. Or at least on a t-shirt. I hate giving patients more than one diagnosis for their presenting illness. It annoys me.

Thanks to Pubmed, I often get to tie everything together.

The patient is admitted with flank pain, malaise, and a 2 point drop in the hemoglobin. UA/UC is negative, but the CT shows a subcapsular bleed. So the diagnosis is spontaneous bleed.

The patient has cirrhosis and lowish platelets, so sure. It happens

Spontaneous renal hematoma was initially reported by Bonet in 1679. It was later on described by Wunderlich in 1856. Although it may present with "Lenk's triad," consisting of acute flank pain, tenderness, and symptoms of internal bleeding, various presentations have been described in the literature.

1679! I will have to take their word for it; I don't read Latin despite the above quote. And Wunderlich and Lenk are in German. But it appears in the old days anyone could get a triad or a disease. Wunderlich syndrome is spontaneous, nontraumatic kidney bleeding confined to the subcapsular and perirenal space.

I still can't get Crislip's sign into the medical lexicon.

Why do people get renal bleeds?

Regarding etiology, meta-analysis done by Zhang et al. found that 61.5% cases were due to tumors (31.5% malignant and 29.7% benign), 17% cases were due to vascular disease, 2.4% cases were due to infection, and in 6.7% cases it was idiopathic.

They called me as the blood cultures grew K. pneumonia. The CT was interesting. There was undoubtedly a sub-capsular bleed, but the kidney looked inflamed, although radiology waffled.

Since I do not like multiplying entities without necessity, I entered renal hematoma and pyelonephritis into the Occam Machine, aka PubMed. And there are a handful of cases of pyelonephritis resulting in a sub-capsular hematoma. Which was interesting, yet another variation on a theme of infection. Bach was nothing compared to infections.

Now what? If the hematoma is infected, it will be difficult to treat, and there are a variety of other comorbidities that give IR and urology pause about aspiration/drainage. As the patient is doing fine, it is antibiotics, and see how the kidney and bleed evolve.

The got all better.

Rationalization

Urol Ann. 2011 Jan;3(1):44-6. doi: 10.4103/0974-7796.75852. Spontaneous subcapsular renal hematoma: A case report and review of literature. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037002/

J Emerg Med. 2010 Oct;39(4):440-2. doi: 10.1016/j.jemermed.2007.10.042. Epub 2008 Apr 18. Subcapsular renal hematoma complicating acute pyelonephritis https://pubmed.ncbi.nlm.nih.gov/18394849/

Crislip's Sign. http://boards.medscape.com/forums/?128@@.2a32c105!comment=1

POLL RESULTS

I think

• Occam rules 29%
• Hickman rules 0%
• Chaos rules, order is an illusion 57%
• Order rules, chaos is an illusion 0%
• It's an eminence front, it's a put on. https://www.youtube.com/watch?v=rx6Zgz0TZuA 14%

What Are The Odds?

Feb 9, 2021

The patient has a bicuspid valve that gets infected. No surprise. I would bet it is the most common underlying valve abnormality I see with endocarditis in non-IVDU.

The cultures all grew a methicillin-sensitive coagulase-negative Staphylococcus, S. epidermidis, and he was cured with a course of antibiotics.

That was then. This is now. Fast forward three years. He presents with fevers, malaise, and an embolic event to his finger. Again all the cultures grow coagulase-negative Staphylococcus, S. epidermidis, same sensitivities as last time.

What are the odds?

Endocarditis has a

US incidence of 10,000 to 15,000 cases each year.

or

There were 457,052 IE-related hospitalizations in the United States from 2000 to 2011,

That's 45,00 cases a year of native valve endocarditis, give or take.

Others say around 5/100,000, or around 17,000 cases a year, but that is prosthetic and native valve combined.

So not that many.

For predisposing conditions,

bicuspid aortic valve disease affects about 1 to 2 percent of the population.

So maybe 3,500,000 people have a bicuspid aortic valve in the US.

Their risk?

The 25-year risk of IE was 5%±2%.

Or maybe 7000 (3500000*.05/25) cases a year in patients with bicuspid valves. That makes no sense, as that suggests half of endocarditis patients have an underlying bicuspid valve. I must be doing the math wrong.

How about coagulase-negative endocarditis?

Coagulase-negative staphylococci (CoNS) accounts for \<5% data-preserve-html-node="true" of all episodes of native-valve endocarditis (NVE).

Wait. 1 in 20? No way. 500 cases a year in the US? Ten per state per year, not considering population density. Oregon has 3%-ish of the US population. 15 in Oregon. Again, no way.

And how often is endocarditis recurrent in a non-IVDA?

Six patients (4%) had 8 recurrent episodes of IE (1.3% per patient-yea- As is so often with these types of numbers, it is more a rule of thumb than a precise amount.

So what are the odds he would get a reinfection with the same organism on a bicuspid valve? Got me. But small.

Odds of winning Powerball are 1 in 292,201,338.

Like endocarditis, someone wins. Or loses.

Rationalization

Infective Endocarditis Epidemiology Over Five Decades: A Systematic Review https://dx.doi.org/10.1371%2Fjournal.pone.0082665

Risk and outcomes of aortic valve endocarditis among patients with bicuspid and tricuspid aortic valves https://openheart.bmj.com/content/4/1/openhrt-2016-000545

5 Basics to Know About Bicuspid Aortic Valve Disease https://healthblog.uofmhealth.org/heart-health/5-basics-to-know-about-bicuspid-aortic-valve-disease

Incidence of Infective Endocarditis in Patients With Bicuspid Aortic Valves in the Community https://www.mayoclinicproceedings.org/article/S0025-6196(15)00819-8/fulltext

Native Valve Endocarditis Due to Coagulase-Negative Staphylococci: Report of 99 Episodes from the International Collaboration on Endocarditis Merged Database https://academic.oup.com/cid/article/39/10/1527/460385

Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. https://pubmed.ncbi.nlm.nih.gov/25975469/

Long-term outcome of infective endocarditis in non-intravenous drug users https://pubmed.ncbi.nlm.nih.gov/18990319/

POLL RESULTS

Statistics

• makes my head hurt 19%
• are misunderstood by 4 out of 3 44%
• are just another way to mislead 11%
• under and over estimated most of the time 19%
• are an unnatural act 4% Other Answers 4%
• All the above - and what are the chances of that?

Not Everything is Infectious

Feb 11, 2021

The patient is admitted with sepsis: fever, fluid responsive hypotension, mild leukocytosis, and, most worrisome, decreased vision.

Occasionally, bacteremia seeds the eyes, and the results are not good. I suppose you could rank organs in order of fretting about the sequella of damage. Perhaps brain, then the eye, then dominant hand. I would rather lose 20% of my liver or lung than 20% of any of those.

Ophthalmology sees him, and it is bilateral panuveitis.

The patient is on azathioprine and some mab, Anakinra, for seronegative RA when admitted, but otherwise healthy.

He has the four-star workup for infection, and I am betting on either Bartonella or Toxoplasma as both have a predilection for the eye, and there are new cats in the household.

Nope. Everything is negative: cultures, serologies, 16S on the vitreous, and a Karius test.

Because of the turnaround time, he goes home on a hodgepodge of antibiotics until the tests return. If it had not been an eye infection, I would have stopped the antibiotics far earlier. But I am going to be extra-cautious with both eyes involved.

I see the patient in follow up and there has been a slight change in his vision for the better, but otherwise, he is fine. His arthritis is a bother, still quite painful and migratory, but no red, hot, swollen joints.

Except.

His ear has been red and tender for the last week. It looks like someone had been in a boxing match, the ear red and swollen, except for the lobe. It looked like a sharp line had been drawn across the ear, across which the redness would not cross.

That was odd. There is no way he could get cellulitis on the antibiotics I had him on. Being, as you know, an Occams kind of guy, I put uveitis and relapsing polychondritis into the Googles. And there are cases. Google it yourself if you are interested, but one report notes

Ocular manifestations of relapsing polychondritis occur in 60% of patients. Uveitis is a rare symptom, sometimes severe, which can lead to blindness.

Other ocular manifestations include

... proptosis, lid edema, episcleritis/scleritis, corneal infiltrates/thinning, iridocyclitis, retinopathy, and optic neuritis.

Now, if I had just answered 'B' on every rheumatology questions when I took my medicine boreds all those years ago, I might have had a higher score on the subsection. Let's just say rheumatology isn't my strongest topic. But a quick read of relapsing polychondritis seemed to fit.

So I called his rheumatologist and told her what I suspected, with a grain of salt from the not so rheum expert.

But what patients don't tell you. With that in mind, the patient noted with direct questioning by the rheumatologist that he had an episode of lots of sneezing several months prior and blew a hole in his nasal septum.

So relapsing polychondritis it was. I do not know about you, but there is little that gives more satisfaction than getting to the diagnosis before anyone else.

Rationalization

[Bilateral uveitis in relapsing polychondritis. A case report]. https://europepmc.org/article/med/15976722

Ocular and Systemic Findings in Relapsing Polychondritis https://www.sciencedirect.com/science/article/abs/pii/S0161642086336959

POLL RESULTS

The organ I would least like to lose 20% of is

• brain 44%
• eye 13%
• hand 10%
• tongue 5%
• skin 23%

Never Saw It From That Mechanism

Feb 23, 2021

Took more time off last week. I hope to do more of that in the final few years of my career. As I have noted before, no one in the history of the world has ever said on their deathbed, "Doc, I wish I had spent more of my life at work." I really enjoy ID, but medicine can be all-consuming if you are not careful.

The patient has a week of fevers, rigors, and malaise. She gets blood cultures, and they all grow S. gordonii. With a prosthetic aortic valve, the diagnosis is prosthetic valve endocarditis.

There is no "good" reason for endocarditis except his good dentition. As mentioned in a prior post, S. gordonii has a prediction for clean teeth.

S. gordonii therefore can rapidly colonize clean tooth surfaces, and S. gordonii along with related organisms comprise a high percentage, up to 70%, of the bacterial biofilm that forms on clean tooth surfaces.

No good deed ever goes unpunished.

She was otherwise non-focal on ROS and exam. CXR shows little: just a touch of fluid in the right costal phrenic angle. No surprise in someone with CHF. That means there are about 75 ml in there, 25 more than usual. Nothing to worry about.

Three days later, she has increasing shortness of breath, decreased breath sounds, and pleuritic chest pain. Repeat CXR now shows a huge effusion that on CT is multiloculated.

It's pus, grows S. gordonii and requires a VATS. Once drained, still no pulmonary infiltrates.

I have seen a ton of empyemas over the years, and they have either been from a pneumonia or some sort of fistula to the pleural space. This was neither. I have never seen an empyema whose only risk was from bacteremic seeding of a pleural effusion.

Is that a thing? Not really.

There is, maybe, a spontaneous bacterial empyema in cirrhotics:

However, since 1976, numerous reports have described an unusual form of pleural fluid infection in the absence of underlying pneumonia. This condition has been mainly seen in patients with decompensated cirrhosis. In view of the absence of a contiguous infection, and perhaps by analogy with spontaneous bacterial peritonitis (SBP), the term spontaneous bacterial empyema (SBEM) was coined for this disease.

But I can find a few odd bacteremia cases (Shewanella and S. typhi) seeding the pleural space and none from the viridans Streptococci or as a complication of endocarditis without septic emboli.

As best I can tell, a pleural effusion is not a risk for empyema without a concomitant pneumonia.

I don't quite believe my search results, but as best I can tell, this is a first.

The patient did fine with antibiotics, VATS, and time.

Rationalization

More is not better http://boards.medscape.com/forums/?128@@.2a828e61!comment=1

POINT: Does Spontaneous Bacterial Empyema Occur? Yes https://journal.chestnet.org/article/S0012-3692(15)38342-2/fulltext

COUNTERPOINT: Does Spontaneous Bacterial Empyema Occur? No https://journal.chestnet.org/article/S0012-3692(15)38343-4/fulltext

Probably Reinfection. But...

Feb 25, 2021

One year ago, the patient had endocarditis, diagnosed and treated at another hospital. The reason was a bicuspid aortic valve. He received the standard course of therapy and was declared a cure.

Fast forward to now. A month of low-grade fever, malaise, night sweats, and the sudden onset of painful finger led to the ER. The finger looked classic for an embolic event. There was a vegetation on his aortic valve, and he was admitted.

All the blood cultures, like a year ago, grow the same Staphylococcus epidermidis.

Hmm.

This should be a new infection, given the time from the last treatment. Right? But what are the odds of getting a rare cause of native valve endocarditis twice? Probably on order of winning the lottery. It doesn't happen often, but there are winners. Stuff happens.

But I wondered, for entertainment's sake, if this could be a relapse. Years ago, I had an IVDA with Abiotrophia endocarditis who I thought I had cured. Lost to follow-up, she presented a year later with the same organism in her blood. In this case, she was in fulminant heart failure and died and essentially had no valve. The Abiotrophia had been likely slowly destroying her valve for a year. That patient was asymptomatic for 11 months, likely in part because of heroin use.

But.

Prosthetic valve coagulase-negative endocarditis can present up to a year after the valve is placed and the organism is, presumptively, acquired at the time of surgery.

And prosthetic joint infections due to coagulase-negative Staphylococci can fester for years before becoming clinically apparent.

So is this a relapse or reinfection? In the few studies, it is definitional. If it is more than six months since treatment, it's reinfection/recurrence, not relapse.

One study found

The median time between the initial episode and repeat episode of IE was 9.1 months (25th--75th percentile, 3.8--24 months; range, 2.1--64 months).

And using molecular methods to compare organisms, found the clinical definition was unreliable. But. Most of the infections were with S. aureus and I would think, like coagulase-negative Staphylococcus, you would get reinfected with your own flora, as the authors realized.

We recognize that one cannot exclude the possibility of a reinfection (as opposed to a relapse) with the same microorganism in patients who have an additional episode of IE due to a microorganism with an identical PFGE pattern. For example, reinfection of a hypothetical patient with a persistent colonizing strain of S. aureus could give the erroneous impression of relapse.

S. epidermidis does like to hang out in biofilms, doing nothing, not dividing, not dying. Biofilms are usually associated with medical device infections. But a search finds that recently there has been a flurry of studies evaluating biofilms in vegetations as one reason why endocarditis is difficult to treat.

...recent advances in molecular microbiology techniques that have uncovered a plausible explanation for this resistance to treatment: the recently discovered social behavior of some microbes, in which colonies form a nearly impenetrable barrier around themselves called a biofilm.

And a place for S. epidermidis to lie low for a year?

I don't know. I can't imagine a S. epidermidis lying dormant in a vegetation for a year, but that may be more a limitation of my imagination than reality.

Relapse? Could be.

Rationalization

Relapses, recurrences, valve replacements, and mortality during the long-term follow-up after infective endocarditis https://doi.org/10.1067/mhj.2001.111952

Repeat Infective Endocarditis: Differentiating Relapse from Reinfection https://academic.oup.com/cid/article/41/3/406/340878?login=true

Dormant bacteria within Staphylococcus epidermidis biofilms have low inflammatory properties and maintain tolerance to vancomycin and penicillin after entering planktonic growth https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170483/

Current Hypotheses in Cardiac Surgery: Biofilm in Infective Endocarditis https://doi.org/10.1053/j.semtcvs.2015.12.005

Getting senile. I forgot I wrote about this case, from a different perspective, two weeks ago. What Are The Odds? It is why I call my wife honey. Can't remember her name. Sigh.

All's Quiet on the COVID Front

Mar 4, 2021

It has been weirdly quiet at work. The same thing occurred after the summer COVID surge. As the COVID cases fell, there was no surge in other ID cases. So I have had little to write about. Just aren't any cases.

It is peculiar. It has been noted that stroke and myocardial admissions fell during COVID. Exactly why is uncertain. I would wonder if it is due, in part, to a decline in infections.

Infections are inflammatory, inflammation is prothrombotic, and that leads to vascular events.

Systemic or localized infections increase the risk of thrombosis ~220 times and are independent risk factors for thromboembolic diseases such as deep vein thrombosis (DVT)/pulmonary embolism (PE) as well as cardiovascular (myocardial infarction) and cerebrovascular events (stroke)

COVID restrictions, masking, social distancing have led to a decline in influenza and other respiratory infections. As examples.

The global decline in influenza virus circulation appears to be real and concurrent with the COVID-19 pandemic and its associated community mitigation measures. and

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, we were surprised to find that all other respiratory viral infections fell precipitously.

Influenza is particularly good at causing cardiovascular events. And fewer viral pneumonias would lead to fewer secondary pneumonias.

So maybe fewer URIs, fewer vascular complications, fewer secondary infections.

And I am going to see fewer nosocomial infections since elective surgeries were cut back.

But.

It seems infections that would not be COVID-related are down as well, or maybe it is my imagination. I haven't done a formal survey. But I usually have 3 or 4 IVDA at any time with endocarditis or other complications. Last two weeks? One.

And this happened right after the summer spike: a lull in IVDA infections.

There is the issue of excess deaths, and during COVID, the number of excess deaths (what a weird term) has been more than COVID deaths, suggesting that we are undercounting COVID deaths. Or there are other causes of excess deaths. Overdose deaths are way up in the US and Oregon.

From January to June 2020, at least 339 people died of a drug overdose in Oregon. This figure is nearly 40% higher than the number of overdose deaths from the same period in 2019 and represents an increase of nearly 35% from the previous six-month period, July to December 2019.

But I can find no data on infectious deaths in that population.

So perhaps my IVDAs are succumbing to overdoses instead of infections.

But whatever the reason, infections seem down.

It occurs to me the title may be bad luck (spoiler alert) given that the protagonist is killed on the last day of WW1. On the other hand, I doubt we will ever be rid of COVID, so I am safe.

Rationalization

Reduced Admissions for Cerebrovascular Events During COVID-19 Outbreak in Italy https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031293

Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848062/

Decreased Influenza Activity During the COVID-19 Pandemic United States, Australia, Chile, and South Africa, 2020 https://www.cdc.gov/mmwr/volumes/69/wr/mm6937a6.htm

Precipitous Fall in Common Respiratory Viral Infections During COVID-19 https://academic.oup.com/ofid/article/7/11/ofaa511/5936123

Overdose Deaths Accelerating During COVID-19 https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html

Oregon trends with US in accelerated drug overdoses https://www.oregon.gov/oha/ERD/Pages/Oregon-trends-with-U.S.-in-accelerated-drug-overdoses.aspx

POLL RESULTS

As best I tell

• non COVID infections are the same 4%
• non COVID infections are down 11%
• only IVDA infections are down 0%
• bird feathers are down 22%
• my optimism for the future is down 56% Other Answers 7%
• , , down dooby doo down down. Breaking up is hard to do.

Lots of Fretting Comes to Naught?

Mar 9, 2021

The patient was initially admitted with an acute coronary syndrome, they call it. Some sort of heart issue I am lead to believe; it required coronary stents. She was discharged home, only to return ten days later with a red, hot, swollen abscess in the antecubital fossa where an IV had once been.

And clotted stents that required unclotting.

And MRSA in all the blood cultures.

On day one, day 3, day 4, and day 5.

Sustained MRSA is the sine qua non of endocarditis, so that was the presumptive diagnosis.

In addition to the positive blood cultures, the fevers persisted.

I had lots of fretting.

S.aureus is otherwise known as coagulase-positive Staphylococcus, so did the stents clot because they were infected with MRSA. It happens, albeit rarely. I have yet to see a case and to be picky, a sustained MRSA is the sine qua non of an endovascular infection.

And he developed a pericardial effusion and a progressively thick pericardium.

Was this a slowly progressive bacterial pericarditis, the clinical course slowed by the antibiotics? Or had the infarction been seeded with the MRSA? I had one Streptococcal infected MI that blew out slowly.

Or had the MRSA seeded elsewhere? Around half of metastatic gram-positive infections are clinically silent.

And she went into complete heart block. From a myocardial abscess or infarction? She needed a pacemaker, just the kind of device you want to implant in a patient with an uncertain number of potential MRSA infections.

So we temporized while we went looking.

TEE: no vegetations and the area around the stents, the pericardial fluid, and MI didn't look infected.

CT: thick pericardium, but the Hounsfield units suggested it wasn't pus.

I even ordered a PET CT. There is a lot of literature on the utility of PET scans with S. aureus bacteremia and I felt for sure something in and around the heart would glow. Nope. Quiet. But there was a clinically silent lumbar discitis.

The blood cultures were negative from day 6, and the fever resolved. So out of the woods? I still fret.

There is one case of a stent false-negative PET scan due to prior antibiotics. Like this patient.

And the blood cultures? The problem with S. aureus bacteremia is that on occasion, the bacteremia is intermittent:

Intermittent bacteremia occurred in 13% (140/1071) of episodes. A single negative BC on days 1--3 had a predictive value of 87%--93% for resolution of bacteremia, although this was improved if all BCs collected within the same day were considered...Intermittent negative BCs are common in SAB.

I remain uncertain how to incorporate this study into my practice, but I am by no means certain the MRSA is gone/controlled, but what more to do?

So she received her need pacemaker, is now on a long course of antibiotics, and ID parameters are all improving.

Most of my blog entries are nice and neat: a diagnosis, a culture, and a treatment. This case is more representative of my service: uncertain diagnosis, uncertain diagnostics, and uncertain treatment.

Rationalization

18 F-FDG PET/CT Optimizes Treatment in Staphylococcus Aureus Bacteremia and Is Associated with Reduced Mortality https://pubmed.ncbi.nlm.nih.gov/28336786/

Retrospective Study Comparing WBC scan and 18F-FDG PET/CT in Patients with Suspected Prosthetic Vascular Graft Infection https://www.ejves.com/article/S1078-5884(19)30033-4/fulltext

Intermittent Negative Blood Cultures in Staphylococcus aureus Bacteremia; a Retrospective Study of 1071 Episodes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047948/

Wrong Again

John Doe, a middle-aged, apparently homeless male, is admitted with fever, seizure, and unresponsive.

I wondered. Why John Doe? Shouldn't a male be John Buck? And females Jane Doe? And if the ICU has multiple unidentified patients admitted, is it a herd?

Where did the name come from? According to Wikipedia, it dates back to the 1300s for placeholders for fictitious plaintiffs, with the fictitious defendant being Richard Roe. It's the Roe in Roe v Wade. I never noticed that. But why those names are not known. I wish we had stayed with the ancient Romans "Numerius Negidius" and "Aulus Agerius."

Squirrel.

He had a high blood alcohol level and a marked leukocytosis. The next day, the blood cultures and spinal fluid are growing gram-positive cocci in pairs and chains.

S. pneumoniae, I said on the phone when called for the consult, is classic in alcoholics. I'll be there in a couple of hours; the current antibiotics are fine.

When I got to the ICU, I had two extra pieces of information.

LP shows 3000 WBC, a glucose \<10, data-preserve-html-node="true" and a protein >1000. And the organism was identified as Group B Streptococcus.

That, I said, is odd for bacterial meningitis. The WBC is too low; it should be more like 10,000.

And a protein that high? That's epidural abscess levels of protein due to CSF obstruction. Needs an MRI.

Which showed? No epidural.

But the concept of worrying about an epidural abscess with a sky-high protein is still valid. I did find the average protein to be 418 in bacterial meningitis with

Protein values of greater than 1,000 mg/dl, reported in 8% of cases in Merritt and Fremont-Smith's review, were often associated with spinal subarachnoid block.

The only time I have seen a CSF protein that high with no epidural abscess is a case of TB meningitis where there was so much protein the CSF had the consistency of jello. Not sure, beyond alcohol use, why he has this infection.

GBS meningitis in adults mainly occurs in those with underlying conditions such as immunocompromised state, CSF leakage, and endocarditis.

In Asia, it is associated with the consumption of raw or undercooked farmed fish.

He has none of the above.

So it was antibiotics and time.

Rationalization

Cerebrospinal Fluid Analysis https://www.aafp.org/afp/2003/0915/p1103.html

LETTER TO THE EDITOR Community-acquired Group B streptococcal meningitis in adults https://www.journalofinfection.com/article/S0163-4453(20)30121-3/pdf

Community-acquired group B streptococcal meningitis in adults https://pubmed.ncbi.nlm.nih.gov/31830496/

POLL RESULTS

With my conclusions, I am

-often wrong for the right reasons 25% -often right for the wrong reasons 25% -infallible 0% -insufferable 21% - often in error, but never in doubt 25% Other Answers 4% - no longer relevant.

Antibiotic Advice From Who?

Mar 15, 2021

You don't tug on superman's cape You don't spit into the wind You don't pull the mask off that old lone ranger And you don't take antibiotic advice from surgery

Jim Croce. Sort of.

The patient is admitted over the weekend for cellulitis. She has a superficial ulcer on her shin from an injury six months ago that has been slow to heal. She also had changes of chronic venous insufficiency changes on her legs.

There was the abrupt onset of a rapidly spreading erythroderma with a fever. No pus. No abscess.

So she is started on...

Vancomycin.

Sigh.

Clinically it was one of 6 things: Group A strep, S. pyogenes, Group A Streptococcus or Streptococcus pyogenes. Maybe Group G Streptococcus or MSSA.

Cefazolin should have sufficed.

Overnight it had spread.

Of course, it did. It takes time to get therapeutic on vancomycin. Infection always worsens for a day before it stabilizes. And vancomycin stinks on ice. The patients fever fell, and she felt better.

But clindamycin was added.

And the next day, it had stabilized. But the WBC had increased. So surgery was called in cases it was necrotizing fasciitis. It wasn't. But surgery -surgery, mind you- suggested a carbapenem. And meropenem was added.

Weekday rolls around, and they call me.

Sigh.

I would not recommend getting cardiology advice from an Ob doc. I would not ask an ID doc how to remove a gallbladder. And don't get antibiotic recommendations from surgery.

What most infections need is an exposure history before antibiotics and patience once proper antibiotics are started. She had neither.

It looked all the world like a typical Group A Streptococcus infection, but on direct questioning, she has a dog that licks her wound almost daily. I have discussed that issue before. Clinically, there is no difference between Streptococcus and Pasturella. Although, I have it my head that Pasturella is unique and notable for rapid spread, I cannot confirm that factoid, so it is likely not true.

Cultures are all negative so far, but I simplified antibiotics to kill Streptococcus and Pasturella, and she continued to improve.

Rationalization

It Takes a Licking http://boards.medscape.com/forums/?128@@.2a83e095!comment=1

POLL RESULTS

I get antibiotic suggestions from

• Up To Date 15%
• ID docs 22%
• a random MD found in the hall 7%
• drug reps 7%
• magic 8 ball 33% Other Answers 15%
• I give it!
• our homepage guidelines
• nobody. Yet. Someday it'll be too late, and wrong.
• my ID PharmD

temp space

Magic 8 Ball

May 24, 2021

Spent the last week hiking in Eastern Oregon. Beautiful territory. Part of the time was in Harney County, which has the highest COVID rates in the state, despite appearing empty. While the vaccination rates are 30%, those without masks were 99%. Eye roll. Harney County. Come for the scenery. Go home with COVID.

I have my biases. One is that vancomycin is an antibiotic of (mostly) historical interest. As I have said many a time, while there is no such thing as a strong, big gun or powerful antibiotic, there are antibiotics that stink on ice. Vancomycin is the archetype. I only use it when I have perfect source control of MRSA bacteremia or for trivial infections. Otherwise, I go with either ceftaroline or daptomycin.

You may rely on it.

The patient has MRSA endocarditis with multiple metastatic abscesses, source control for which is problematic. With an MIC to vancomycin of 1.0, I opt for ceftaroline and the patient does relatively well for 4 weeks.

Then, routine CBC has a WBC of 0.5. It's the ceftaroline.

Without a doubt.

The overall rate of incident neutropenia was 10%--14% with ≥2 weeks and 21% with ≥3 weeks of ceftaroline exposure.

So he is changed to daptomycin and does well for 48 hours until a fever. Neutropenic fever means cefepime, so the weekend crew added cefepime. The next day, the blood cultures grow E. coli.

Outlook not so good.

Which raises two issues.

One of the common errors I see is when a patient has a fever several days after discontinuation of antibiotics, the discontinued antibiotic is resumed.

Nope.

Don't count on it.

Presuming the patient had an appropriate course of an appropriate antibiotic for a well-defined infection....hahahahahahahaha

I kill me. Like that ever happens.

But presuming the above to be the case, the patient likely has acquired new bacteria that is resistant to the prior antibiotic. Use it and lose it.

Change antibiotic classes.

You may rely on it.

So I changed the patient to meropenem pending susceptibilities.

But the answer to the other question is more opaque. Can the cefepime perpetuate the ceftaroline-induced neutropenia?

Reply hazy, try again.

It would depend on how ceftaroline leads to neutropenia, and

The mechanism whereby ceftaroline (or other cephalosporins) leads to neutropenia remains unclear; however, both immune-mediated and bone marrow effects (via immune-mediated processes and/or direct damage to the myeloid cell line) have been proposed

And

Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative β-lactam.

I can find little on whether other cephalosporins would be safe. Cefepime and ceftaroline do share similar R1 side-chains and that may determine problems with cross-reactivity. Maybe.

But another reason in this patient to avoid cefepime. But it would be better if it were

Without a doubt.

Rationalization

J Antimicrob Chemother. 2016 Jul; 71(7): 2010--2013. High incidence of neutropenia in patients with prolonged ceftaroline exposure https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896407/

Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes. Open Forum Infectious Diseases, Volume 6, Issue 5, May 2019, ofz168, https://doi.org/10.1093/ofid/ofz168

A Review of β-Lactam--Associated Neutropenia and Implications for Cross-reactivity https://doi.org/10.1177/1060028020975646

Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity Pharmacy 2019, 7, 103; doi:10.3390/pharmacy7030103 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789778/

Magic 8 Ball https://www.ifate.com/fateball.html?fb=1

500 Days of COVID

Jun 03, 2021

I realize I have not written much about COVID 45. This blog usually concerns the little, odd, interesting features of infectious diseases. While a disaster, there has not been much with COVID that has been all that odd or interesting to write about. The literature/science has been changing so fast that most entries would be outdated as soon as published.

But it has been 500 days of COVID, and it looks like we are nearing the end of the initial bolus of disease. So what have I learned/concluded? My take. Your mileage may vary.

Not that COVID is ever going to go away. A remarkable number of Americans prefer being vulnerable to COVID, able to get ill or pass it on to others and kill them. Huge swaths of the world will remain unvaccinated and a reservoir for the reintroduction of the virus into susceptible populations, with localized outbreaks and deaths. Whether it will be seasonal or a constant background problem, I, of course, do not know but would bet on a combination. COVID is here to stay.

Back in January, I thought we would have 1.5 million deaths after a year and a half. Thanks to vaccines and masks, I am so glad to be wrong, although we are approaching 600,000 dead. About the same number from the 1918 flu pandemic. Or about the number of combat deaths in all our wars combined (666,442). Compared to flu, it took COVID 6 times as long in a population about three times greater than 1918 to kill that many people. So as pandemics go, not that virulent. I still fret about the next influenza pandemic.

Also, note I did not use the descriptor 'only' in front of the number of dead. I am a John Donne kind of guy of the classic version, not the 2020 version. Anyone who considers human death and suffering, even one, as an only, is an expletive of your choice.

The whole idea of 'natural' herd immunity is ludicrous. There is no such beast. To my knowledge, we have never had natural herd immunity to any infection. The only time you get herd immunity is when everyone who can be vaccinated is vaccinated. Since there is currently no way the US will ever get close to herd immunity, COVID is here to stay.

Here is a rule about treating acute viral infections: the antiviral needs to directly interfere with an important viral metabolic pathway and needs be given within 72 hours of onset.

You could predict that azithromycin and lopinavir and hydroxychloroquine, and ivermectin would do nothing. It was like cold fusion. Despite being bogus based on basic science, people came up with all sorts of reasons they might, might, just might have efficacy. They didn't because they can't. So much time and money wasted.

It is said those who do not remember the past are doomed to repeat it. Plus ça change, plus c'est la même chose, dude.

It was so nice to take the hydroxychloroquine away from patients in whom we know it works and saves lives and waste it on COVID, thanking them for their sacrifice. I never prescribed any of the above. It was stupid. And I don't do stupid.

I still think remdesivir is more placebo than not. The problem with most of my patients is they present at day 7 or more of illness, long past when I would think any antiviral would work. And there is no way you can tell clincally if remdesivir is effective given the drawn-out nature of the disease. So I have to trust the literature, such as it is, that remdesivir is beneficial. And always remember Most Published Research Findings Are False.

I was surprised when convalescent serum turned out to be a bust. But upon reflection, I shouldn't have been surprised. By the time most people received serum, they were likely on their way to their own immunity. Again, too little too late, the motto of COVID therapy. Except for dexamethasone and IL-6 inhibitors. The late pro-inflammatory stage, and the long haulers, have been a curious and unexpected COVID manifestation

Until last year, I considered the word from the CDC to be law, and I took what they said at face value. No longer. Now it is trust, but verify.

The whole disinfection of everything was shown early in the pandemic to be medical theater, but it is still being done.

I remember arguing with a radiologist in February 2020 that they didn't need masks; the CDC said COVID was spread by contact and masks are not needed. That was, of course, male cow manure and a lie for the wrong reasons.

If I had given it any thought, instead of taking the CDC at their word, I would have realized that the only way that a virus could spread so fast in Wuhan was respiratory.

As the man said, "There's an old saying in Tennessee---I know it's in Texas, probably in Tennessee---that says, 'Fool me once, shame on... shame on you. Fool me---you can't get fooled again."

I also think the whole droplet/aerosol/6 feet apart is worthless medical theater.

From a hospital infection control perspective, the difference between aerosol and droplet spread is important. There, you have a patient in a bed who is not moving and controlled air handling. There, six feet for droplets makes sense to protect staff. The vector is still, their pig-pen like COVID haze controlled.

In the real world, the haze of COVID moves around with the vector, and chaotic airflow will take droplets and aerosols willy nilly through the indoor environment.

I am six feet apart in line at the store, and the air conditioning breeze pushes the COVID laden air from the person behind me into my space, but then I move forward 6 feet into the COVID haze of the person in front of me. 6 feet my ass.

To my mind, it is more about the density of vectors. The lower the density of people, the less chance someone will have COVID, and the more likely the COVID haze will disperse before I wander into it in search of beer. What the optimal density would be would depend in the incidence of COVID but I think just me in the store is about right.

It is why it is masks that are important indoors for preventing spread. But outside? Wearing a mask outside when all alone is stupid, and as I mentioned, I do not do stupid. I have a three-mile walk every day in the neighborhood and do not wear a mask. Or golfing. Or hiking. I rarely encounter anyone. If I see someone coming, I cross the street. If for some reason I encounter a group of people who I can't avoid, I participate in a little medical theater and wear a mask.

What astounded me the most in the COVID pandemic? The incompetence and lies of the executive branch of government or was the willingness of large numbers of Americans to participate in behaviors that sickened and killed hundreds of thousands of their fellow citizens?

Good question.

But neither should not have surprised me. The US always been happy to have large numbers of people die from preventable causes.

It has always been the problem with infection control: the person who passes on the MRSA or the COVID never sees the consequences of their actions. All 560,000 plus deaths from COVID occurred because someone passed it on. But who? Usually, we never know. In a perfect world, those who fail to practice infection control would be the ones to get the infection, but as President Carter once noted, "There are many things in life that are not fair."

There was a period of time when masks in the hospital were optional, and I would ask those not wearing a mask why they wanted to kill me. At the time, given my age and comorbidities, I estimated a 5% chance of death. I would not hold a gun to my head if I had a 1 in 20 chance of pulling the trigger and blowing my brains out

But I got lucky, and infection control works. Despite all the COVID patients I saw, I never acquired COVID, and now, with the vaccine, my chance of dying of the disease is zero.

I am still amazed at how rapidly we understood COVID. The HIV pandemic started when I was a medical student, and it took years to know the cause and find a treatment. COVID took months. And to get safe and effective vaccines so fast? Incredible.

But my main reaction to the COVID pandemic is despair. COVID was, in the scheme of things, simple to understand and control.

Huge numbers of Americans don't want to bother with science or reality. So when the next pandemic hits, one with a 5 or 10% mortality rate, the corpses are going to pile up. And we will let it happen.

And compared to what we need to do to combat global warming? COVID has been trivial.

So we are doomed. As a people. As a society. As a democracy. As a planet. I'll likely be dead before the worst of it, but the children born today?

Doomed.

Clusters Instead of Chains

Jun 07, 2021

The patient has a month of progressive failure to thrive and a cough. Work-up is negative as an outpatient, and he is given a week of prednisone for RAD. He improves, then worsens.

Seen in the ER, he is afebrile and has a negative exam except for a murmur from his 5-year-old bioprosthetic valve. The worry is an occult malignancy, so among other studies, he has a pan-scan.

At the same time, blood cultures drawn the preceding day are growing gram-positive cocci in clusters.

The CT looked like classic embolic lesions to the kidney.

So I said it is prosthetic valve endocarditis, probably coagulase-negative Staphylococcus or, given how indolent his infection is, a Micrococcus, which forms tetrads, kind of cluster. Although the preliminary molecular ID said none of the above, it is not always correct.

But what else causes gram-positive clusters?.

Gemella morbillorum.

That forms clusters? Yep. Pairs, short chains, or clusters.

Are there other pathogenic gram-positive cocci that make clusters? I can't find it.

Gemella endocarditis is rare, with 65 cases in the most recent review. I do not think I have ever seen a case. A TEE showed nothing evil, but I suspect all his vegetation had moved on to his kidneys.

He has done well on penicillin and a short course of gentamicin.

But why do some gram-positives grow in clusters and others grow in chains?

Streptococci grow in one plane because they spit down the middle, but with Staphylococcus

The organisms appeared to divide in three alternating perpendicular planes, with sister cells remaining attached to each other after division. The resulting point of attachment was usually not exactly at the point corresponding to the center of the previous septal disk. Moreover, sister cells often changed position with respect to one another while still remaining attached. These factors are apparently responsible for the irregularity of staphylococcal clumps. Studies with penicillin and the examination of thin sections in the electron microscope confirm the conclusion, based upon light microscopy, that successive divisions in S. aureus occur in perpendicular planes.

It remains round throughout replication, unlike other bacteria which elongate, as

S. aureus lacks an apparent elongasome machinery.

That was 1976. Nothing from 1976 has stood the test of time. Now?

Although this mode of division was proposed over four decades ago, the molecular mechanism that ensures this geometry of division has remained elusive S. aureus cells do not regularly divide in three alternating perpendicular planes as previously thought. Imaging of the divisome shows that a plane of division is always perpendicular to the previous one, avoiding bisection of the nucleoid, which segregates along an axis parallel to the closing septum. However, one out of the multiple planes perpendicular to the septum which divide the cell in two identical halves can be used in daughter cells, irrespective of its orientation in relation to the penultimate division plane. Therefore, division in three orthogonal planes is not the rule in S. aureus.

as

...although a plane of division is always perpendicular to the previous one, it is not necessarily perpendicular to the penultimate division plane. As a consequence, the majority of S. aureus cells do not divide in three alternating orthogonal planes.

There is even a cool video, with a paltry 254 views, demonstrating how S. aureus is a cluster-bug. There are 9000 ID docs in the US; you would think more would have been curious about why some gram positives are chains, others clusters, and found the video.

There are similar studies on Micrococcus but not Gemella.

Those studies explain what Staphylococcus does, not why. Is there a benefit to three-dimensional replication? Insert NSFW comment of your own devising here.

The non-standard cross-section of the septum in S. aureus distinguishes it from other model organisms and indicates that not all peptidoglycan insertion occurs at the leading edge of the septum in this species prompting the development of a new model for how peptidoglycan is synthesised during the cell cycle ). This is likely advantageous to the bacteria, enabling more biosynthetic enzymes to work on the cell wall without steric hindrance.

I assume every function in an organism has an evolved reason, so an improved peptidoglycan synthesis works for me.

But for S. aureus, I wonder if clustering has a more pathogenic/malign origin. As to Gemella? All I can find is it is a cousin of Staphylococcus, in the order of Bacillales and the family of Staphylococcaceae. So perhaps something similar.

Rationalization

Avicenna J Med. 2019 Oct-Dec; 9(4): 164--168. Published online 2019 Oct

3. doi: 10.4103/ajm.AJM_3_19 Gemella endocarditis: A case report and a review of the literature https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796301/

Geometry of cell division in Staphylococcus aureus. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC234932/

eLife. 2018; 7: e32057. Published online 2018 Feb 21. doi: 10.7554/eLife.32057 Molecular coordination of Staphylococcus aureus cell division https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821461/

Nat Commun. 2020 Aug 14;11(1):4097. doi: 10.1038/s41467-020-17940-9. Reassessment of the distinctive geometry of Staphylococcus aureus cell division https://pubmed.ncbi.nlm.nih.gov/32796861/

Geometry of Staphylococcus aureus cell division https://www.youtube.com/watch?v=2Bw-SKu7pbQ

On The Water Front

Jun 09, 2021

Getting old? Stinks. On ice. Last week I had night call and then on-call this weekend. And I am pooped. I have nowhere the stamina I did even last year. And time off does not energize me for work; it only makes me want more time off.

My big mistake was marrying a younger woman. She is not medicare eligible until 2024, so I am working for health care for the next several years. I so hope Biden lowers the age of eligibility to 60. If so? As much as I like ID, I'm outa here. Some day, you youngsters will understand.

The last twenty-four hours gave me a twofer.

Both patients were obese with chronic edema. Both had chronic skin breakdown. One has cirrhosis, the other diabetes.

Both are admitted for SIRS and a lower extremity cellulitis.

Both had gram-negative rods in the blood.

In my youth, I had been taught that gram-negative rods do not cause cellulitis in normal hosts, and when they do, it is a necrotizing infection. Not so.

Over the years, I have seen an assortment of cellulitises (celluliti?), diffuse erythroderma, in relatively normal hosts. What they all had in common was obesity, although I can't find this association in the PubMeds.

For erysipelas, 4.6% of 607 patients had positive blood cultures, of which ...11% were Gram-negative organisms. For cellulitis, 7.9% of 1578 patients had positive blood cultures of which ... 28% were Gram-negative organisms.

But what is the difference as a clinician between a cellulitis and an erysipelas? Cellulitis is deeper than erysipelas, but I can't tell that on the exam.

The most characteristic finding in erysipelas, the sharply defined and slightly elevated border, helps to differentiate this entity from cellulitis, which has an indistinct border.

In chronic edema patients, no one can tell. I do not find it a useful distinction. Is it diffuse erythroderma, abscess, or necrotizing? That is what I care about. I agree with the uselessness of

the current distinction between cellulitis and erysipelas

for predicting the microbiology.

The diabetic grew Pseudomonas aeruginosa; the cirrhotic Stenotrophomnas maltophilia.

What do those have in common? Water. So I bet my resident that the Stenotrophomnas maltophilia patient bathed in untreated well water.

Bingo.

As did the Pseudomonas aurgenoasa pateint.

Stenotrophomnas maltophilia hospital outbreaks traced to tap water are common, but I was surprised to find no cases associated with wells. There are many articles on Pseudomonas in well water, and while water exposure is classic for a variety of Pseudomonal infections, none are specifically from well water.

Wells are a common water source outside the Portland metro, and the water is never treated, but I have yet to get confirmatory cultures from the well. I probably have half a dozen-odd gram-negative infections over the years I have blamed on untreated well water.

So maybe it is not the thing I think it is. Or perhaps I'm the only one who routinely asks about water sources?

Rationalization

Journal of Infection Volume 64, Issue 2, February 2012, Pages 148-155 Journal of Infection Review A systematic review of bacteremias in cellulitis and erysipelas https://www.sciencedirect.com/science/article/abs/pii/S0163445311005512

Hippokratia. Jan-Mar 2018;22(1):23-28. Gram-negative bacteria as emerging pathogens affecting mortality in skin and soft tissue infections https://pubmed.ncbi.nlm.nih.gov/31213754/

Biomedical Research (2017) Volume 28, Issue 20 Isolation of Stenotrophomonas maltophilia from water and water tap https://www.alliedacademies.org/articles/isolation-of-stenotrophomonas-maltophilia-from-water-and-water-tap-8980.html

Overview of Water-related Diseases and Contaminants in Private Wells https://www.cdc.gov/healthywater/drinking/private/wells/diseases.html

Local Warming

Jun 14, 2021

The patient, a methamphetamine user, is found in a parking lot, rolling on the ground, completely disoriented.

Transported to the ER, he is febrile to 102, hypotensive, and in mild MOSF. His WBC is 42,000.

The examination is negative for infection. Standard workup is negative for infection; clear CXR, normal CT of chest/abdomen and pelvis. The panscan in the donut of truth is standard. Blood cultures are negative at 24 hours so they call me.

I find nothing and he had defervessed and improved with fluids and on antibiotics. His WBC had dropped to 38,000.

The one thing I didn't mention is that occurred on the hottest day of the year, at least so far. It was 90 degrees out. Fahrenheit, not centagrade. Global warming isn't that bad. Yet.

You people in Phoenix or the South many poo poo that 90 isn't all that hot, but we in the Great Pacific NW do not have to deal with heat. I recently saw an article about the pros and cons of moving to Portland. One of the cons was that air conditioning is not standard in housing. Yep. That's gonna change.

What kind of infection can cause this kind of leukocytosis with a non-focal exam and studies? Meningococcus and S. pyogenes in my experience, but he isn't sick enough.

So, I wondered, heat stroke?

He is homeless with mental illness, so access to water and food is a challenge. So he could have been volume short aka dehydrated.

So I Googled it.

Meth both mimics and increases the risk for heat stroke:

Death as a consequence of methamphetamine can occur in one of three ways: heart attack, heat stroke, or suicide.

and

Four workers who died of heat stroke had a documented history of alcohol abuse or high-risk drinking. In three other heat stroke fatalities, methamphetamine was detected in postmortem toxicology tests.

And while meth can cause a leukocytosis, it is more in the 10,000 range.

But.

Heatstroke can cause a leukemoid reaction. And this drives me nuts. When I saw the consult and did the search, I found two cases of heat stroke with a WBC in the 30,000 range. Can I find them now? No. Am I using the same search criteria? Yes. This happens all the time. The google search at one moment leads to different results at another.

Oh, wait. Here it is. From UpToDate:

Laboratory studies may reveal coagulopathy, acute kidney injury (acute renal failure), acute hepatic necrosis, and a leukocytosis as high as 30,000 to 40,000/mm³.

Like this patient.

A perfect storm for heat stroke: a hot day in a heat intolerant Oregonian with little access to water and a meth habit. And a leukemoid reaction as a consequence.

He improved with supportive care.

Rationalization

Richards JR, Farias VF, Clingan CS. Association of leukocytosis with amphetamine and cocaine use. ScientificWorldJournal. 2014 Jan 22;2014:207651. Source

Tustin, Aaron W. MD, MPH; Cannon, Dawn L. MD, MS; Arbury, Sheila B. RN, MPH; Thomas, Richard J. MD, MPH; Hodgson, Michael J. MD, MPH Risk Factors for Heat-Related Illness in U.S. Workers, Journal of Occupational and Environmental Medicine: August 2018 - Volume 60 - Issue 8 - p e383-e Source

I Could Not Stay Away

Aug 23,2021

About two months ago Medscape had a change in direction for their blogs. It was not a direction I wanted to go. Nothing personal, but I had pretty much done things my way for 12 years and, being a control freak like most ID docs, did not want to give up control.

There were no hard feelings.

Well.

It would have been nice if, after 12 years, 1400 or so entries, and maybe a million words, they would have said thanks for all the work.

Nope.

If there is one lesson I cannot seem to learn is that organizations will never, ever reward hard work and devotion. Don't let the man fool you into trust and loyalty. It will never be repaid in kind. But then I am just a snowflake.

I thought it would be a good time to retire the blog, and given there were two or three people who actually seemed to notice, it seemed like a reasonable decision.

But. But. But.

I kept seeing cases and would think, "This would be a great case to blo-oh wait, I'm not doing that any more."

And I found I missed writing the blog. ID is easy and fun to write about, different from fiction which is hard and fun. I quit writing at Sceince Based Medicine in part because I grew bored, but I have yet to get bored with ID.

I also realized that blogging was too valuable a way for me to learn. The process of writing helps imprint concepts in my mind. It is why when I have a resident on service, I usually write my own notes rather than attest them. The process of putting pen to paper, or electrons to screen, crystalizes the case for me.

How often I will put up a post remains to be seen as I am now working three-quarters time. Once or twice the weeks I work, probably. And I am half considering blogging on topics unrelated to ID. Or not. I don't know. We will see. As Cartman would say, Whatever, I do what I want.

So, like Michael Corleone, I'm back in, at least for the next 3 years, 10 months, 6 days, 23 hours, 12 minutes, and 31 seconds.

Not the First Case Ever

Aug 23, 2021

The patient is an almost healthy female who, three days prior to admission, had her right groin catheterized as part of examining her coronary arteries.

She came in with fevers, rigors, and a red hot swollen groin.

Cellulitis.

OK.

She was started on vancomycin, and the next day I was called when both sets of blood cultures had gram-positive cocci in chains.

By the time I saw her, the erythroderma and pain at admit had nearly resolved. Kind of quick to get better.

It's going to be a Group A Streptococcus or maybe another Streptococcus. And there are the occasional pseudoaneurysms after angiography, so beware the Enterococcus.

We looked. No pseudoaneurysm.

But the next day, the organism was identified as Abiotrophia defectiva. That's odd. A quick Pubmed found no cases of Abiotrophia defectiva as a cause of cellulitis, and it is a mouth organism. Yeah, the mouth and rectum are connected, but it seemed a stretch.

The closest was

We report a case of infective endocarditis (IE) caused by Abiotrophia defectiva in an 8 year-old boy presented initially with left ankle cellulitis and fever.

Went back to the patient armed with the microbiology. No murmur, no emboli, no nothing except on direct questioning he had three teeth extracted several days before the catheterization.

And the TEE showed a small vegetation on the aortic valve. While not the firest case ever of primary Abiotrophia cellulitis, it is the first case in an adult of endocarditis due to Abiotrophia defectiva presenting as cellulitis. I'll take it.

Rationalization

Iatrogenic femoral artery pseudoaneurysms--a review of current methods of diagnosis and treatment https://pubmed.ncbi.nlm.nih.gov/18996260/

Infective Endocarditis due to Abiotrophia defectiva presenting as Ankle Cellulitis https://www.semanticscholar.org/paper/Infective-Endocarditis-due-to-Abiotrophia-defectiva-Subhi-Yaqubi/a6f827a53def581f9ed509ea93fd665425ad5d8d

I Love Me That High Tech

Aug 25,2021

"My god, what is this, the Dark Ages?" Bones McCoy. The Voyage Home

For most of my long and storied career, ID has been pretty low-tech. I did an H&P, then hoped we grew something on agar plates. It has been that way forever. In the 21st century, we have finally had access to technologies that allow for the routine diagnosis of some of the oddest infections.

The patient is an elderly male, mostly healthy, who has two months of intermittent fevers, rigors, sweats, and progressive malaise.

Outpatient work has yielded nothing, and by the time he is admitted, there is quite the list of negative studies, from cultures to TEE to a CT of the chest/abdomen/pelvis.

Always a challenge to add to an extensive workup. So back to the H&P to give me a hint as to where to go.

When I see him, there is little in the way of exposures for odd infections, and his exam is negative.

But he looks ill, and his CRP and ESR are markedly elevated.

The only thing of note is several years ago, he had an extensive repair of his aortic arch and descending aorta, and he is full of endovascular graft.

So it is between a vasculitis of some sort or perhaps a graft infection. Reviewing the CT with radiology, the aorta/graft doesn't look infected, but it doesn't look not infected. Too complicated to tell.

So I order a PET CT, as one of many studies notes

FDG-PET scanning showed a better diagnostic accuracy than CT for the detection of vascular prosthetic infection.

I always think FDG stands for fudge, as in "present or deal with (something) in a vague, noncommittal, or inadequate way, especially so as to conceal the truth or mislead." Like most medical studies. Except the PET.

Bingo was his name-o. One section of the arch glowed like Chernobyl. As best could be determined, the infection was in the old clot between aortic and graft and involved the graft. But from what?

And several years out for surgery, was this a new infection, or has it been festering since the repair?

So with negative blood cultures, I sent off a Karius test. Lots of Legionella micdadei DNA. I did not see that coming.

There are a grand total of 2 cases of Legionella causing aortic graft infections, both pneumophilia

So a worlds first: Legionella micdadei aortic graft infection, diagnosis made possible by high tech. Although, I still want Dr. McCoy's tricorder.

Why? No reason I can find. No good water exposure outside of Portland city water and no similar case from the time of his surgery that would point to an infection acquired in the OR.

On a quinolone, symptoms markedly improved (macrolide intolerant), but how long to treat is problematic since

The findings of this meta-analysis confirm the positive association between fluoroquinolones and the development of aortic aneurysm or dissection. The data tend to show that this association may be majorly driven by aortic aneurysm.

Does it matter, given his aorta is mostly replaced/repaired? Got me.

Rationalization

Accuracy of FDG-PET--CT in the Diagnostic Workup of Vascular Prosthetic Graft Infection https://www.sciencedirect.com/science/article/pii/S1078588410003345

Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis https://www.ingentaconnect.com/contentone/ben/chamc/2019/00000017/00000001/art00004

Really. What Else Could It Be?

Aug 20,2021

Quos Deus vult perdere, prius dementat (Those whom God wishes to destroy, he first deprives of reason) US Motto 2020-2022

This isn't going to be a COVID entry, and the quote has nothing to do with what follows. I was going to modify it to suggest being smug about one's diagnostic abilities is a sure path to disaster (Those whom God wishes to destroy, he first makes diagnostically smug). But I'm one smug sob at times, and, hey, what is the point of false modesty? Sometimes I do know what I am doing.

If you include my fellowship years, this is my 35th year in the ID biz. And I will let you in on a little secret if you promise not to tell anyone.

ID just ain't that hard anymore. Every consult has three questions that need answering: what do they have, why do they have it, and how best to treat it. I can usually figure that out in about 10 minutes. Even with the most complicated case, if you can separate the wheat from the chaff, it can generally be figured out in under 30 minutes. The rest of the consult is dotting t's and crossing i's, making sure you don't get blindsided by something unexpected. You have to be complete even when you have the answer upfront. Just in case.

You have probably noticed that ID docs do love to brag about much time they spend on a case, but it is time mostly spent reviewing information that doesn't matter. The vast majority of cases can be figured out in 10 minutes and summed up in a sentence or two if you know what is and is not relevant to the case at hand. But it took me 20 plus years, a quarter of my life, to get to that point. Until then, ID was hard.

As a fellow and resident, I remember how my ID attendings would generate an extensive differential diagnosis for cases but never commit. I always construct three lists for every patient. What they have. What I don't want to miss, even if unlikely if it could kill/harm the patient. And what is the cool diagnosis?

But I like to commit to a diagnosis. I love it when the venn diagram of the three lists has the same diagnosis at the top. Frequently in error, never in doubt, that's my motto. But as I have mentioned in the past, everyone remembers Babe Ruth pointing to right field and hitting a home run. No one remembers he led the league in strikeouts. So I commit. And it impresses the hell out of people when you are right,

Case in point, an FUO.

Four months of roughly one a week rigors, fever, sweat.

CBC/Comp/Blood cultures/CT CAP as an outpatient all normal except for a mild anemia.

So right away, any number of infections, presuming it is infection, are off the table. Few diseases go on that long, and with that pattern. Two, maybe three,

PMH: recent Bells palsy.

Now we are down to one possible disease.

Further questioning shows he visits the US NE frequently, and while he does not remember any tick bite, his Bells palsy was evaluated, and he had a positive Lyme serology, which had been treated.

So in about 8 minutes, I was down to the one disease this was likely to be. Ticks spread more than one disease with a bite. So.

Babesia?

Malaria was also on the list, but a case of suitcase malaria seemed less likely. Suitcase malaria is where an infected mosquito hitches a ride in a suitcase and infects someone in a non-endemic area. I have yet to see a case.

I did the rest of the usual H&P to be complete. Nothing. No other exposure history to put him at risk for odd infections.

So sent off a thick and thin smear and bingo was his name-o. Babesia. The first case that I have ever diagnosed.

But really, what else could it be? See? ID is simple. After spending most of your adult life at it

He got all better on Babesia therapy.

Rationalization

Origin and prevention of airport malaria in France https://onlinelibrary.wiley.com/doi/10.1046/j.1365-3156.1998.00296.x.

Coinfection by the tick-borne pathogens Babesia microti and Borrelia burgdorferi: ecological, epidemiological and clinical consequences https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713283/