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June 17th, 2018

Remembering Robert H. (Bob) Rubin, Father of Transplant Infectious Diseases

During my ID fellowship, Robert (Bob) Rubin was my very first attending. It was the transplant service in July, and Bob and I would round with the surgeons each morning.

Early each morning. That was part of it. We needed to be there with them, before they disappeared to the OR. If we weren’t there, he explained, we might as well be invisible — they wouldn’t trust us.

This was one of Bob’s many strengths as an ID doctor, his ability to connect with our surgical colleagues. So many of us timidly leave our consult notes in the patient chart, hoping the surgical team will listen to our recommendations.

No such passivity from Bob. He spoke right to them.

It didn’t hurt that he had extraordinary clinical instincts, and was one of the most naturally intuitive clinicians I’ve ever worked with. His assessments were lightning quick, an especially notable trait in a specialty often prone to (endless) rumination and equivocation.

And, like a good surgeon, Bob was direct about everything. He knew what he knew — and told you — and knew what he didn’t know, and acknowledged this too. No hedging.

He was also by nature an active doer rather than a passive observer. In clinical care, he frequently used war and sports metaphors. No surprise — surgeons really like an ID doctor like this!

Bob is best known for his contributions in transplant infectious diseases, a field he practically created. Many of the concepts we now take for granted as accepted standard of care either originated with him or were greatly amplified by his skillful and prolific teaching.

Here are a few of these key principles (with thanks to Jay Fishman and Francisco Marty for contributing):

  • The predictable timeline after transplant for the occurrence of certain opportunistic infections.
  • The “net state of immunosuppression”, which is the sum of pharmacologic, nutritional, and anatomic factors contributing to infectious risk.
  • The compromised host as the “sentinel chicken” (a.k.a. “canary in the coal mine”) for environmental hazards.
  • The “therapeutic prescription” — he wrote: “The close linkage of infection with the nature and intensity of the immunosuppressive program has led to the concept of the therapeutic prescription. This has two components: an immunosuppressive one to prevent or treat rejection and GVHD, and an antimicrobial one to make it safe. Implicit in this statement is the recognition that changes in the immunosuppressive strategy must trigger changes in the antimicrobial program.”
  • A refusal to define a specific length of antimicrobial therapy at the outset of treatment — treat “long enough”, he would say.
  • The immunomodulating effects of certain opportunistic infections, in particular cytomegalovirus.
  • The use of “preemptive” treatments in patients at high risk for developing infectious complications — here’s his classic review of the concept.
  • Corticosteroids are like credit cards — patients (and doctors) get immediate satisfaction, but the bill comes at the end of the month. He often called them “feel goods”.

During fellowship, I remember presenting him a case one day of a man who’d had a renal transplant several years before, and was doing great — on low dose cyclosporine and prednisone, with normal renal function. He’d been struggling for the past week or so with intermittent headaches, and his primary care doctor was concerned — could this be something infectious?

My differential diagnosis was absurdly broad, including practically every known opportunistic infection that can cause headaches — listeria, cryptococcus, nocardia, aspergillus, mucor, toxoplasmosis. Cripes, I might have even mentioned acathamoeba.

Bob sat and politely listened, then kindly said — “Very good — but I’ll bet you it’s none of these things. He just doesn’t fit the pattern.”

His point — this patient was too healthy for these infections. The kind of transplant patient who usually gets these infections has been treated for repeated bouts of rejection, or experienced CMV reactivation, or has been heavily exposed to some pathogen, or is nutritionally compromised, or worst of all, all of the above — these are the “awful-awfuls”.

“If you want to send a serum cryptococcal antigen, go ahead,” he said. “But it will be negative.”

I sent it, and of course Bob was right — test negative. Turns out the patient had stopped drinking coffee because of heartburn, and was suffering from caffeine withdrawal. No acanthamoeba.

Bob died earlier this month after a lengthy illness. We will all miss him.

June 7th, 2018

What’s Your Favorite Off-Patent Antibiotic Brand Name?

National Library of Medicine

Each time the FDA approves a new drug, they also approve a new brand name.

The FDA and other regulators want something safe. They critically want to avoid names that sound or look similar to existing drugs, which could trigger medication errors. And names that imply an ingredient or an action not supported by clinical data are also off-limits.

But what if you’re a pharmaceutical company? You probably want something snappy and memorable, something that becomes practically synonymous with treatment of the condition. In this review of the drug brand-naming process, Prozac (for fluoxetine) meets all these criteria perfectly.

Marketing bliss achieved!

To counteract this commercial force, I commonly correct ID fellows, residents, and students when they use brand instead of generic names of antimicrobials.

Some would call this pointless. Others, pedantic.

Said no one, ever: Thank you so much, Dr. Sax, for correcting me when I said Z—n instead of piperacillin-tazobactam — or “pip-tazo”, as you seem to be so fond of saying.

In compensation for these years of haranguing, I hereby present for your listening pleasure a podcast on antimicrobial brand names. Joining me is the always lively and scintillating Dr. Raphael (Raphy) Landovitz, an Associate Professor of Medicine at UCLA and a longtime friend and ID colleague.

In order to avoid infringing on complicated patent law, we stick with off-patent drugs. And since people get their podcasts from all sorts of places, here are several options:

If you have your own favorite brand names, that’s what the comments section is for — but remember, off-patent only!

June 3rd, 2018

My Dog Louie Was Attacked by Another Dog — He’s Fine, I’m a Mess

Louie, by Ellie Deneroff

On a cool morning recently, I was taking my dog Louie for his morning walk.

We headed to a small local park, a place we’ve been hundreds of times in his 5-year life.

He loves it. Lots to sniff. A chance to trot around without his leash. Perhaps a soggy tennis ball to chase, after I’ve given it a quick toss. (They must taste great, yum.) Squirrels and birds in abundance — these make him quite vigilant.

It was early, so no one was around — at least for the first 5 minutes or so.

Then, another dog arrived, perhaps a bit bigger than Louie (maybe 25 pounds), very cute and energetic.

Then this exchange:

“How’s your dog’s disposition?” asked the owner.

“He’s fine with dogs his size,” I said.

Off came the other dog’s leash.

Here’s what happened in the next 5 seconds:  Once the leash was off, the other dog made a beeline for Louie, who tried to run away — but he’s not much of an athlete.

Then, Louie made a sound I’d never heard before. You can’t really describe how terrible this sound is unless you hear it firsthand. My friend Susan made an excellent analogy — it’s like what you hear during a car accident when you’re in the car versus when you just hear about someone else’s accident. Yikes.

I ran over to pick him up. He had a sizable gash on the left side of his snout; blood was dripping into his mouth.

We took him to the local animal hospital. They admitted him, put him under anesthesia so they could wash out the wound, closed it in two layers with four stitches. Many hours later they discharged him home to us, his very distressed owners.

I felt horrible. Why didn’t I realize that when the person asked me about Louie’s disposition, this was a red flag for rowdy behavior? What if Louie is permanently scarred, either physically or emotionally? What if he gets a life-threatening infection from Capnocytophaga canimorsus?

(Promised the NEJM Journal Watch editors I’d put a little ID in here. Done!)

In short, how could I have let this happen? 

Dogs are like toddlers — they rely on us to keep them safe, because they’re not good at this part of survival. Examples — Louie will occasionally bark loudly at dogs big enough to eat him for breakfast. I’m referring to really giant dogs, they’re practically bears. Our friend’s dog has never met a skunk he didn’t try to chase, much to everyone’s dismay. One of Louie’s brothers (Arlo, he lives on our block) sometimes chases cars. Not smart, dogs!

But, just like our two-year-old kids, dogs are very good at making us want to take care of them — which is why canines have survived all these thousands of years.

Because unlike the toddlers, dogs don’t advance past this dependent stage. The deal we’ve made with them over evolutionary time is that we provide food, shelter, and safety; in exchange they give us back unconditional love. I’d clearly let down my side of the deal, at least on this day — and it felt awful.

The good news is that Louie bounced back like a champ. Aside from 24-hours of post-anesthesia fogginess, and undoubtedly embarrassment over having to wear the Cone of Shame for a few days, he’s been fine. He’s been back to that park several times, no detectable PTSD, no wariness.

He doesn’t even seem to mind when we call him Scarsnout. That’s because he’s a good dog.

Now I’ve got to be a good owner.

Area Dad Chased by Ferocious Beast.

Area Dad Chased by Ferocious Beast.

Posted by Paul Sax on Thursday, May 17, 2018

May 28th, 2018

Predatory Journals Are Such a Big Problem It’s Not Even Funny

I’ve made fun of academic spam numerous times on this site.

It’s those emails from dubious “predatory journals,” written in cheerful but awkward prose, with flowery praise and open invitations to submit research on various scientific topics.

You know, the emails that start:

Dear Dr. Paul E.
Greetings for the day!

Most of my coverage has been on how (unintentionally) funny they are. By carpet bombing anyone with a scientific or academic affiliation with these emails, their ability to match content areas with the recipients often misses the mark. For example, I receive an inordinate number of invitations to submit papers to fish-related journals. Go figure.

But there’s a darker side — just like spam of the non-academic variety, the true motivation of these emails is profit. They make their money off publication fees (only revealed after a paper is accepted) and by sponsoring affiliated bogus conferences.

Dr. Sharon Bloom, Executive Associate Editor at Emerging Infectious Diseases, kindly shared with me a presentation she gave this year on the topic at the European Congress of Clinical Microbiology and Infectious Diseases. It outlines in startling detail the pervasiveness of this predatory journal problem, and why it is growing.

One might wonder why the predatory journals have exploded (by some estimates there are more than 10,000), and what some of the hazards are for academic medicine in general, and ID in particular.

Part of why they succeed is because they co-opt markers of credibility, to fool people into thinking they’re the real thing. Journal titles are carefully crafted to sound similar to established, credible journals. Here are a few ID-related publications (from the Hyderabad-based OMICS Group publisher):

  • Journal of AIDS and Clinical Research
  • Journal of Infectious Diseases and Diagnosis
  • Virology and Mycology
  • Advances in Molecular Diagnosis
  • Journal of Bacteriology and Parasitology
  • Journal of Antivirals & Antiretrovirals
  • Archives of Parasitology

The first one is a particular problem for this readership, as it draws many highly regarded research groups who consider it a good back-up option for their research. You might think the awkward introductory text on their homepage would raise suspicion:

Acquired Immune Deficiency Syndrome (AIDS) is a disease caused due to HIV virus that affects the human immune system tremendously eventually leading to death. HIV is considered as one of the fatal cause of death in the present times.

Good grief. Sounds like a 6th grade science report — grade B-minus.

Predatory journals have other tricks. Many make up their own impact factors. Distinguished names may appear on the front page as members of the editorial board — though it appears that some of these individuals are listed without their even knowing. Indeed, some might not exist at all — in this sting from last year, a fictional researcher with dubious credentials applied for and was accepted to numerous editorial boards.

Some predatory journals advertise that they are “Indexed in PubMed,” because selected articles are deposited into PubMed Central under open access policy agreements with certain funders. Take a look again at the Journal of AIDS and Clinical Researchthe appearance of these articles in PubMed gives little clue that this is not a legitimate journal.

After submission to these journals, there’s no or trivial peer review, no obvious quality control, and no editorial board oversight. A paper submitted to the International Journal of Advanced Computer Technology consisted of just 7 choice words — and was accepted. Another person wrote a paper on nuclear physics using his phone’s autocomplete function — also accepted. In case you want to do the same, I’ve embedded the how-to video at the bottom of this post.

Further evidence of shallow (if any) peer review is that some papers are submitted and then accepted for publication within 1-2 weeks — an impossibly fast turnaround time for real peer review, revision, and resubmission.

Here’s are a few examples Sharon shared with me:

As Editor of Open Forum Infectious Diseases, I can assure you that these rapid turnarounds are only possible if the “peer review” is a rubber stamp — one that reads “Accept”.

And speaking of OMICS — here is Sharon’s summary about this particular publisher (slide #6/43), for which the word prolific barely does it justice, and this review should make legitimate researchers, funders, and publishers squirm:

The predatory journals also thrive by exploiting the academic’s need to publish — leading to what the New York Times called “a new and ugly symbiosis”:

Many faculty members — especially at schools where the teaching load is heavy and resources few — have become eager participants in what experts call academic fraud that wastes taxpayer money, chips away at scientific credibility, and muddies important research.

But it’s not just poorly resourced schools. There are numerous publications in these journals from highly-esteemed institutions (including one on the East Coast that begins with “H”), as well as many studies that cite funding from federal agencies.

In short, these journals represent a profitable and exploitative fraud — as bad as the Nigerian Prince who wants to give you money (provided you share your bank account number), or a phishing scheme that takes control of your computer and its passwords after you click a provided link.

So what should we do? Here’s some excellent advice from Michael Lauer, NIH’s Deputy Director for Extramural Research:

Simply put, publish where you cite. If you are not familiar with a particular journal, then consider speaking with your local academic librarian as well as consulting resources from the publishing community (e.g. Think Check Submit) and the federal government (e.g. Federal Trade Commission).

If that’s too difficult, take a look at the graphic at the top of this post, which just about says it all.

(Graphic courtesy of Madhu Pai; slide Sharon Bloom, both with permission.)

May 20th, 2018

Why the Dolutegravir Pregnancy Warning Is Important — and What We Should Do Now

Last week, in response to newly available surveillance data, multiple agencies issued a warning about the HIV integrase inhibitor dolutegravir (DTG) and pregnancy. The warnings cite an increased risk of neural tube defects in babies born to women who became pregnant while receiving the drug.

From the U.S. Department of Health and Human Services:

The concern stems from a preliminary unscheduled analysis of an ongoing NIH-funded birth surveillance study in Botswana, which has reported an increased risk of neural tube defects among infants of women who became pregnant while taking DTG-based regimens. The study reported 4 cases of neural tube defects out of 426 infants born to women who became pregnant while taking DTG-based regimens. This rate of approximately 0.9% compares to a 0.1% risk of neural tube defects among infants born to women taking non-DTG-based regimens at the time of conception.

The U.S. Food and Drug Administration, World Health OrganizationUnited States President’s Emergency Plan for AIDS Relief (PEPFAR), and European Medicines Agency issued similar statements.

There are several reasons why this warning is important — and why the best treatment for women with HIV who want children remains an open question.

Since its FDA approval in 2013, dolutegravir has emerged as one of our best antiretroviral agents. It’s highly potent, well tolerated, has few drug interactions, and a high resistance barrier — meaning that even patients with poor adherence rarely if ever develop resistance to the drug.

Not surprisingly, DTG-based treatments are now listed among recommended initial options in all HIV treatment guidelines. In a massive shift away from TDF/FTC/EFV, the tenofovir-lamivudine-dolutegravir single-pill regimen — or “TLD” — is increasingly becoming the default therapy in multiple countries throughout the world.

Based on the widespread and growing use of DTG-based regimens globally, these data on the potential risks of becoming pregnant while receiving DTG have immediate and broad clinical relevance.

This is the case despite the fact that this is a preliminary, early warning signal — one that ideally will either be confirmed or refuted with additional data. According to the PEPFAR statement, the Botswana surveillance study will include an additional 600 more births from pregnant women who were using DTG at time of conception.

So as we await further information, what should we do now?

  • Women with HIV who wish to become pregnant and currently are receiving dolutegravir should be switched to a regimen with a more well-defined safety record in pregnancy. My personal preference would be for tenofovir DF/FTC plus either EFV or raltegravir. Note that neither is a perfect choice — EFV has its own ambiguous history in this context, and raltegravir is also an integrase inhibitor. What if this is a class effect? Bottom line — there is simply not enough systematically collected information on the safety of any HIV regimen taken at the time of conception.
  • Women with HIV who are not interested in having children, but are of childbearing age, should be counseled about this new information. If they choose to be on a DTG-containing regimen, regular use of reliable contraception should be strongly encouraged. For the record, there is very limited information to date about bictegravir.
  • Women who become pregnant while on dolutegravir need to talk with their HIV providers about what to do. This is a tricky clinical scenario, and the one that triggered the safety warning. Although the exposure during conception has already occurred, it would not surprise me if on hearing of these data, women and their care providers would choose to switch to a non-dolutegravir containing regimen.
  • Women starting HIV therapy during pregnancy (that is, after conception) should be treated with a regimen listed in established guidelines. In our clinic currently, this is typically TDF/FTC plus raltegravir. Note that the early data on DTG in this setting are encouraging, as these women started ART after the risk period for neural tube abnormalities; the PEPFAR statement indicates that there are now “more than 2,500 women who began taking DTG after the time of conception” with no reported cases of neural tube defects.
  • Reporting pregnancy outcomes to the Antiretroviral Pregnancy Registry remains an important clinician task. These data are critical to gathering further information about safe ART during pregnancy.

One final point — it’s been clear ever since suppressive ART during pregnancy became standard of care that we could eliminate the risk of HIV transmission to the newborn.

But with that staggering success comes a responsibility — and that is to determine the safest treatment for the uninfected baby.

And while I’ve made fun of the “more research is needed” cliche that academics often bring out when reviewing studies or writing grants, here is one research agenda – the safety of HIV treatment during pregnancy — where further research is absolutely critical.

May 13th, 2018

Why Experienced HIV/ID Doctors Leave Clinical Practice

Three of my good friends — they’re way more than just colleagues after all this time — in the HIV/ID world have left clinical practice recently.

Abigail (Abbie) Zuger, Joel Gallant, and Chuck Hicks, each of them brilliant in different ways, won’t be caring for people with HIV anymore, something they’ve all been doing since the early days of this epidemic.

And I’m sad.

Sure, I’ll be interacting with them professionally in various capacities — but I’m sad for their patients, for their students, for their readers, and also for what this says about our field of HIV/ID in particular, and outpatient care in general.

Abigail (Abbie) Zuger published a piece in the New England Journal of Medicine last week that should be required reading for all experienced clinicians, not just those in the HIV/ID world. Entitled “Moving On”, it describes beautifully the bittersweet realization that her hospital-based HIV clinical practice isn’t what it used to be.

My health is fine, but my stamina is pretty much gone. Our health care system is not kind to the chronically ill and marginally insured, and it is not particularly kind to their doctors, either … the memories of my patients’ decades of life with a dire disease will become theirs alone. Their old paper medical records are off in storage now, and their digital charts are full of inane computer-speak, cut and pasted into gibberish.

Abbie’s obviously a pro when it comes to putting words together, and you can sense the pain it gives her to see complex medical histories destroyed by our cumbersome electronic medical records.

Because if you want to review that history, that story of their “decades of life with a dire disease”? Good luck.

But now the past is accessible only with a call to a warehouse and a long wait. Though many patients, given the time and encouragement, will eagerly talk about their long journey from sick to well, a 20-minute appointment slot allows for neither.

Joel’s no slouch when it comes to writing himself, and sent a brilliant, on-target, and poignant explanation for his decision to leave practice to all his friends and colleagues.

Many of the same themes (our evolving health care system and awful EMR) figured prominently in his decision too:

For us ancient relics of the pen and paper era, outpatient medicine is not what it used to be. We click boxes on computer screens while doing our best to converse and maintain eye contact with our patients. We provide clinically meaningless documentation so we can satisfy billing requirements and meet required “quality measures.” We fight with insurance companies to get patients what they need. We take mandatory on-line training courses to satisfy administrative requirements. We worry about UDS, MIPS, MACRA, CQM, CQI, PQRS, RSR, FQHC, and PCMH. There’s still medicine in there, but it sometimes feels buried beneath the growing bureaucracy and regulatory burden of modern-day healthcare.

He told me recently that in the last month of his practice, he met with an administrator to review his office notes for compliance reasons. He was criticized for not counseling his patient about smoking cessation.

When Joel pointed out the paragraph in his narrative note that discussed this very topic, he was told — “Yes, but you didn’t click the three required boxes, so it doesn’t count.”

That anecdote alone could be Citation #1 in any review of clinician burnout!

Joel also cited the change to the HIV practice in particular. Not too long ago he was using his encyclopedic knowledge of HIV treatment on a regular basis to help his patients.

Today? Not so much.

With so many patients now on stable HIV therapy, and getting older, he found himself “functioning as a primary care doctor and untrained geriatrician,” focusing on “back pain, knee pain, hypertension, and high cholesterol — all important issues, but neither my passion nor my expertise.”

When Chuck left practice, he picked up another theme that helped push him, one mentioned by both Abbie and Joel — the pain and frustration of seeing medicine as a business drive patient care:

An increasing emphasis on medicine-as-a-business makes wRVU’s and provider productivity measures much more important than quality of care and patient satisfaction. Funds generated by our clinic from welcoming and caring for challenging socio-economically deprived patient groups (for example, 340b money) go not to improve the care of these patients, but instead are used to try to balance ever-growing health system budgets.

Probably everyone who reads this blog already knows this, but let me repeat it since it deserves emphasis — HIV care will never be profitable in a system that values high patient volume and procedures, both of which are impossible for a patient population with its disproportionate share of poverty, addiction, and psychiatric disease.

It’s important to mention that the departures of Abbie, Joel, and Chuck from HIV care are highlighted here because I know them so well, and because they were so public with their decisions.

(Each gave me permission to write this, for the record.)

But they are hardly alone — I could have also mentioned Kate, Cal, Ben, Raphael, Corky, Kim, Harold, Andrew, Richard, and many other smart and experienced HIV doctors and researchers, all of whom decided it was time to move on.

It’s an irony, and a painful one, that in the supplement to Journal of Infectious Diseases on Careers in ID, the one on HIV was written by Joel Gallant.


May 6th, 2018

Looking Back on a Decade of Blogging About HIV and Infectious Diseases

Last week, Dr. Wendy Armstrong from Emory kindly invited me to spend some time with their smart, energetic ID fellows.

(See if you can pick me out of the group in the photo at right — hint, I’m the old guy on the left.)

Before the trip, Wendy asked them whether they’d rather hear me give a talk entitled “Evolution of Antiretroviral Therapy” — or alternatively, something about writing this blog, which has just celebrated its 10th Birthday (see colorful banner above).

The email I got back from her was unambiguous:

100% chose the blog.

Although their decision might be viewed as a dismissive of my command of HIV treatment (never!), the good news is that giving this talk gave me a chance to reflect on the 10 years of the blog’s existence.

Before going through the data unearthed by our crack team of research scientists, a little bit about its beginnings. Inspired in the late 2000s by the writing that exploded on the internet about everything, I pitched something similar to the folks at NEJM Journal Watch

It would be about ID, HIV, and whatever else happened to be swimming around in my head on any given day I had time to write something. That was it.

Fortunately, they said yes — thank you! I am also grateful to the community of readers who show up here regularly, interact in the comments section or on Twitter, and teach me (and other readers) so much.

Let’s move on to the data, all of it 100% verified by the Centers for Disease Control and Prevention and the World Health Organization:

We’re collaborative and hard-working clinicians.

Of course there have been challenges. Finding good copyright-free images is always tricky. Who wants a frivolous lawsuit because we happened to use a cherished (and legally protected) picture?

This concern explains the 100% legal but strangely artificial stock images that show up here periodically — which I enjoy mocking whenever possible.

Probably the most common question I get asked by colleagues is “Why do you do that?” Usually I answer with a superficial, “Because it’s fun,” but on further thought, it’s more than that.

As you know, most academic writing is quite formal. The writing one does for research papers in particular must include the perspectives of multiple co-authors.

Then, once the journal gets it, it’s further edited to suit their style. By the time of publication, the original text reads like it’s been through a powerful prose homogenizer machine — everyone sounds the same.

Here I can say whatever I like (within reason), include jokes and funny images and videos, and actually sound like myself. It’s a great privilege, and a true joy.

So to Matt O’Rourke, Catherine Ryan, Kristin Kelley, Amy Herman, Kelly Young, and Bob Dall — all at NEJM Journal Watch — I thank you again.

And here’s my latest sports discovery, Flyball.  Hey, what a perfect name!

April 29th, 2018

ID Learning Unit: Clinically Important Streptococcal Infections You Need to Know

As mentioned last week, I’m currently attending on the general medical service, a chance to brush up on non-ID clinical skills, and more importantly, to work with smart, energetic house staff and medical students.

Not surprisingly, there’s a wide range of clinical ID on this service, and this year we’ve had a rash of streptococcal infections.

(Get it — “rash” and “strep”? Ha ha ha, medical puns are so funny.)

These cases motivated the following summary of clinically important streptococcal infections. They’re worth reviewing because they are common and can be severe; additionally, streptococcal taxonomy has got to be one of the most complicated, confusing, and ever-changing areas in all of microbiology.

It seems to have always been this way with strep — I remember struggling with the right nomenclature back during ID fellowship, and it hasn’t become easier over time. Some of these bacteria have had many names over the years, all synonymous and used interchangeably in medical conversations and literature without rhyme or reason.

Sorry about that. Maybe we should send a letter of protest to the International Association of Streptococcal Taxonomic Standards, which doesn’t really exist — but if it did, they’d deserve our cranky petition.

Here then, is a “Strep Infections 101” course — the ones you should remember, and why, with perhaps a few fun taxonomic facts thrown in. Fun, at least, to ID geeks like me.

And since I’m neither a microbiologist nor a super-specialist in bacterial infections, apologies ahead of time for any errors.

  1. Invasive beta-hemolytic streptococci:  Named “beta strep” by their characteristic clearing when they grow on blood agar (for some ancient reason called “beta hemolysis”), they are further classified by their Lancefield antigen status, referring to their carbohydrate composition of their cell walls. These include most importantly Strep pyogenes (group A strep, GAS) and Strep agalactiae (group B strep, GBS). The former is the well-known cause of pharyngitis and skin infections — everything from cellulitis to erysipelas to lymphangitis to necrotizing fasciitis (it’s the dreaded “flesh-eating bacteria”). Strep pyogenes can also cause scarlet fever (see rash “joke” above), and is unique among these bacteria in causing rheumatic fever. Strep agalactiae is best known as a pathogen of newborns (and for being difficult to spell) — but with our strategy of giving prophylaxis to pregnant mothers who are colonized with GBS, it’s actually more common now as a cause of invasive disease (bacteremia, sepsis, osteomyelitis) in adults, most of whom have comorbid medical conditions such as diabetes, alcoholism, or liver disease. Three other lettered beta-streps (groups C, F, and G) cause pharyngitis and clinically important invasive infections, but we hardly ever refer to them by their species names — weirdly, just their letter (for example, “beta-hemolytic streptococcus group G”). Therapeutically, a welcome characteristic of all these beta streps is that they remain susceptible to penicillin and most cephalosporins — hooray!
  2. Strep pneumoniae. Once upon a time this would have been listed #1! However, though still one of the leading causes of otitis media, sinusitis, pneumonia, and meningitis, the incidence has dramatically declined due to our two available pneumococcal vaccines. Particularly susceptible hosts include those with defects in humoral immunity or asplenia — myeloma, HIV, certain congenital immunodeficiencies, sickle cell disease, alcoholism. Penicillin susceptibility has gradually declined (though most are still penicillin susceptible), while respiratory fluoroquinolone activity fortunately (and surprisingly) has not, at least here in the USA.
  3. Endocarditis-causing “Strep viridans”:  Normal inhabitants of the mouth, and known primarily as a common cause of endocarditis, the viridans streptococci are actually multiple different species of strep frequently lumped under the pseudotaxonomic name, Strep viridans. Many have alpha (green) hemolysis on blood agar, from which they derive their name (viridis is Latin for green); some have no hemolysis at all. Microbiology purists don’t generally like pseudotaxonomic names, and hence your lab will report something more specific than Strep viridans, e.g. Strep mutans, Strep salivarius, Strep mitis, etc.
  4. Also endocarditis-causing Strep bovis — I mean Strep gallolyticus: I nearly put Strep bovis in the above group since it has also become a pseudotaxonomic name; turns out these bacteria previously identified as Strep bovis are actually multiple different species — Strep gallolyticus, Strep infantarius, probably others. Since I don’t really understand all this, and only have so much time in the day, I was heartened to read the following in a recent review: “The history of the Streptococcus bovis group is complicated and confusing due to conflicting classical distinctions based on imperfectly differentiating phenotypic attributes and due to modern disagreements concerning the optimal molecular methods for identification to the species level.” That’s for sure! Endocarditis with Strep bovis (ok, Strep gallolyticus) is most famously associated with colon cancer — a fact that almost 100% of even apathetic medical students know. The penetrance of this bit of microbiology trivia might even surpass medical students’ knowledge of listeria. Which makes me wonder — why are some random facts so memorable? And will this sticky Strep bovis knowledge persist with the new name?
  5. Abscess-forming streptococci — Strep anginosis, Strep intermedius, and Strep constellatus:  Formerly known simply as Strep milleri (those were the days), these streptococci also turn out to be multiple different species, and are now named after one of the three principal isolates, Strep anginosis — hence the term Strep anginosis group is preferred over Strep milleri. In addition to Strep anginosis, you might also find Strep intermedius or Strep constellatus — all three are common causes of dental, lung, liver, brain, and other abscesses. (These species also may have subspecies, but I’m not going to go there. You’re welcome.) As with the beta streps, they have retained penicillin and cephalosporin susceptibility — ceftriaxone is the drug we most commonly use for treatment.

There are, of course, numerous other streptococcal infections, but these are the most common ones on a general medical service.

Plus, it’s time to watch a big inflatable duck rolling down a highway in Des Moines.

April 22nd, 2018

Some ID Stuff We’re Talking About on Medical Rounds — with Bonus Andy Borowitz Podcast

Sam approaching a “scent detection box.”

As an infectious diseases specialist attending on the general medical service each year, I am the beneficiary of a wonderful knowledge exchange.

The smart house staff and my generalist co-attending teach me the latest about hyperkalemia, anticoagulation, anemia, alcohol withdrawal, acute renal injury, COPD, atrial fibrillation, pancreatitis, asthma, diabetes, and congestive heart failure — to name a few of the non-infectious issues that come up routinely during inpatient care.

For example, I am now quite comfortable saying HFpEF — which, if you haven’t done inpatient medicine in a while, is pronounced “HEF-PEF,” and most certainly did not get mentioned a single time during my residency training.

And what do they get in return? A bunch of infectious diseases snippets, factoids, random comments, and (I hope) clinical pearls, such as the following:

Meanwhile, in other news, there’s this podcast — highly recommended and entertaining!

Friends: ten years ago, I had a near-death experience (seriously). Dr. Paul Sax, an esteemed expert in infectious…

Posted by Andy Borowitz on Thursday, April 19, 2018

And note, not a single mention of an antibiotic.

April 16th, 2018

Hepatitis C Positive Organ Donors — Coming Soon to a Transplant Center Near You

There’s one immutable fact in solid organ transplantation — the number of patients awaiting transplant exceeds the number of available organs.

This shortage means that ethical, medically safe strategies to increase the donor pool are always a high priority.

One such strategy would be to allow transplants from people who have chronic hepatitis C.

If the thought of transplanting an HCV-infected organ into an uninfected recipient gives you pause, you’re not alone — the practice is explicitly discouraged in some transplant guidelines.

However, HCV today is an entirely different beast than when these guidelines were crafted. Treatment is now astoundingly safe and effective, with over 95% of patients cured, typically with 8–12 weeks of simple therapy.

Not surprisingly, transplant programs are now studying the safety of conducting transplants from HCV-infected donors into HCV-uninfected recipients, then treating with HCV therapy.

While published data are still relatively sparse, two small studies in renal transplant recipients (here and here, 10 patients each), showed that HCV treatment at the time of transplant or shortly after is safe and effective. None of the 20 patients developed chronic hepatitis C.

Now a third study (led by my colleague Ann Woolley), has just been presented at the annual meeting of the International Society for Heart and Lung Transplantation.

In this trial of lung and heart transplant recipients, 33 patients received organs from donors who were HCV viral load positive; an additional 8 came from donors who were HCV antibody positive but viral load negative. The former group received an abbreviated 4-week course of sofosbuvir-velpatasvir right after transplant; the latter only received treatment if they became viremic (none has to date).

With the caveat that the study is ongoing, thus far the the regimen has been well-tolerated, with no one developing chronic HCV.

Not surprisingly, several other hepatitis C donor protocols are starting, but it’s not rocket science to predict their outcomes. HCV can be effectively treated and cured (or prevented, if you interpret preemptive therapy that way) in transplant recipients, with currently available regimens.

Doing so will greatly increase the pool of available organs. In a tragic silver lining to the horrible opiate epidemic cloud over our country, premature deaths from overdoses may provide life-saving organs to patients in desperate need — organs that previously would have been discarded due to hepatitis C. A paper published today shows that the number of donated organs from overdose deaths has already increased 24-fold since the year 2000 — imagine what this increase would be if organs from people with HCV were permitted.

(Sorry about the silver lining cliché there — but at least I’m in good company!)

Are there remaining research questions with this strategy? Of course — among these include selection of the best regimen, the duration of therapy, management of drug interactions, and cost. Plus, we must recognize that these remain high risk donors who may have other infectious diseases (besides HCV) that will influence transplant outcomes.

But these are answerable questions, with none insurmountable. As noted in this excellent editorial, we’ve long allowed transplants from CMV-positive to CMV-negative patients — and the antiviral regimens for CMV are far less safe and effective than those for HCV.

Can’t you see a policy change coming soon?

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

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