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January 25th, 2024

Printed Medical Textbooks — Going, Going, but Not Quite Gone

Take a look at the things behind my desk at work:

  1. cute photos of family and dog
  2. a bunch of sentimental objects, gifts from grateful patients or colleagues
  3. a smattering of miscellaneous plaques and clocks
  4. pictures of our current (awesome) first-year ID fellows and other stuff
  5. a bunch of books, several of them many inches thick

You may not be familiar with item #5 on this list — those hefty books — so allow me to remind you what they are. Those are medical textbooks. Because if you’re like me, there’s a decent chance you haven’t opened a medical textbook in months, or even years. It’s these that we’ll be chatting about today.

There was a time when consulting these heavy tomes fortified our approach to clinical care on a regular basis. Now, many of us barely ever open them; instead, we look online to recently published papers, comprehensive reviews, the latest treatment guidelines, or other sources to stay up-to-date.

(See what I linked there? Full disclosure, I’ve been a contributor to UpToDate since its very early days, as I’ve detailed previously.)

For evidence supporting this move toward online sources and away from print textbooks, take a look at the results of this poll:

Granted, those who respond to polls on Twixter already live much of their lives online, and hence least likely to turn to an actual printed book. That’s why I repeated it below — different audience, maybe a different response. But still, if you’re a doctor, nurse, pharmacist, or student, chances are excellent you own one or more textbooks, but they’re sitting somewhere in your office, their hundreds (or even thousands) of pages as fresh as the day they left the publisher.

Here are some representative comments I received related to this post:

I literally never use paper textbooks for anything and haven’t for about a decade.

I’m 35 and have a deep nostalgia for physical print books, so I have all my old textbooks (including Harrison’s), but I never use them.

Textbooks in print? Never. Last time over 15 years ago. I do read from the textbooks online.

Have these books in my office shelf for the sentimental value. I have used them twice in last few years.

Wrote a chapter in a textbook. Received free copy. Can’t find a med student around here who will take it off my hands.

Several of these textbooks might include outdated information, pointing to a critical problem with printed books highlighted by Dr. Michael Calderwood:

They look pretty on a shelf but are already outdated by the time that they arrive. Knowledge is changing quickly, and we need readily accessible, expert curated, living documents.

Even worse, how many of us replace the old versions? Guilty as charged — I checked the publication dates on some of the textbooks displayed on my shelf. One is from 2003! Another, 1997! No doubt there are some clinical pearls in these old books, but my advanced math skills calculate that they are decades outdated. Reader beware!

Or maybe your textbook serves another function:

In our fellows’ room, we have an old version of Mandell holding up a computer monitor (which occasionally displays the electronic pdf from the new version). That’s how we use it.

Importantly, there was a vocal contrasting opinion, no doubt representing the 10-28% from the poll. And it’s so interesting that it’s not just older doctors who have this favorable view of printed textbooks! Dr. Courtney Harris, a recent graduate from our ID fellowship program, weighed in with this comment:

I love them. I probably pull one out once a month for hard clinical questions or when I just need a deep overview of something I feel like I really don’t have a good grasp on. Plus I love physical books in general – having a few in my office just gives me joy.

This minority but opinionated group must help sustain the traditional textbook market. Some who continue to use print textbooks say that they can’t learn things as deeply from online sources — a reminder that there’s no right way to learn, just that people take different paths to their own education.

But going back to the numbers from the poll, I maintain that print medical textbook users represent a small (and I suspect shrinking) group. I wonder how long this fragile relationship will continue, especially because writing, producing, and publishing these books isn’t cheap — and neither is their price tag should you want to purchase one.

I confess that exploring this topic fills me with a tinge of nostalgia, one almost reaching melancholy. It has a similar emotional effect to hearing the accounts of other print media dropping in popularity and becoming decreasingly viable economically. Newspapers and magazines (in particular) have been decimated.

Augmenting the sadness is my longstanding participation in writing for some of these texts. For generations of doctors, an invitation to contribute to these pivotal books signaled a true honor. You felt a deep responsibility to research and know the topic thoroughly, to get it just right. After all, someone reading it could make treatment decisions based on your summary of the existing literature. Authorship in these well-known reference books acted as a good way for academic physicians to plant a flag that reads, “I belong.”

Today? A colleague of mine recently submitted a revised version of a chapter to one of these pivotal texts, one that I co-author with him. As it was being revised, I seriously wondered who would ever read it. I can’t imagine the numbers would come anywhere close to a comparable topic in UpToDate, or as covered in a treatment guidelines paper.

I wouldn’t give up on the printed stuff completely, though. Not only are there still people like Dr. Courtney Harris who still value the concrete, real thing you can hold in your hand, but perhaps there’s a burgeoning market:  my 20-something-year-old daughter told me recently how much she loved subscribing to the print versions of two high-quality magazines.

They arrive in her mailbox each week — her actual mailbox, not the electronic one. Imagine that.

Hard-copy, printed medical textbooks -- how often do you use?

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January 2nd, 2024

Reflections on Working in the Hospital During the Holidays

On-service ID team, December 25, 2023

For the zillionth year in a row, I spent the Christmas holiday working in the hospital. For me, it’s not much of a sacrifice — we don’t celebrate Christmas, and my kids are long out of school so the strict limits on when we can take vacation are a thing of the past. But it puts me in a notable minority, as around 90% of U.S. workers have the day off.

So what do we 10%-ers get in exchange for working? Here’s a secret — we get plenty. A brief rundown:

Camaraderie. This is one of the best things — the immediate recognition among those in the hospital that we’re in this together. Take a look at that picture of the faculty and fellows on call. Do those look like unhappy doctors? Importantly, a couple of the members of this quintet do celebrate Christmas, yet made the sacrifice to come in. To them, an especially big thank you!

Continuity. Sadly, illness doesn’t take a holiday and neither do hospitals — they’re a 24/7 business. The patients who must be in the hospital over Christmas are mostly quite sick, or socially disadvantaged, or both. They’re usually pretty upset about having to be there, quite understandably. So they very much appreciate that some of the doctors who were following them before the holidays know them during the holidays too.

Barter. Working Christmas allows us to trade this important holiday for others. For example, I haven’t worked Thanksgiving in years and almost always find a way to get coverage for Passover. Already I’ve blocked off Christmas 2024 as a time both my wife and I will be working — you’re welcome, happy to do it.

Bonus. Several years ago, our division adopted the policy of providing a small bonus to the on-service faculty for working certain important holidays. (Apologies to our residents and fellows who don’t get this. Maybe that will change now that they have adopted a union?) Note that for most salaried workers, it’s typically 1.5 or even 2 times the hourly rate. Believe me, it’s appreciated.

Golden Citizenship Award

Citizenship. Some of the crew on call over Christmas volunteer to do so nearly every year. As the person in charge of clinical scheduling, I hereby give them the Golden Citizenship Award. Mike, Eric, Amy, Anna — you know who you are — thank you! Place this award in a prominent place, it’s quite valuable.

Sustenance. The hospital president every year sends around an email wishing us happy holidays and announcing that lunch and dinner in the hospital cafeteria are free. This year’s entrees were pretty good, both the chicken and vegetarian options, though I wasn’t a big fan of the dessert. But if it’s sweets you’re after, no worries — hospitals are replete with goodies, homemade and otherwise, practically everywhere you go. This year, I arrived on one hospital unit to find gorgeous homemade chocolate chip cookies invitingly set out on a tray with a sign saying, “Take One”; another unit had a huge basket of assorted Lindt truffles. Noticing my rapt attention to the chocolates, a kind nurse insisted I not leave the floor until taking a few. Yum.

Appreciation. If you work over the holidays, you can pretty much guarantee that plenty of people will thank you. Patients, doctors, nurses. Hey, note that even I am thanking people (see “Camaraderie” and “Citizenship”, above).

Learning. Medicine is a lifetime of education! No reason this needs to stop over the holidays, right? Cryptosporidiosis, vascular graft infections, bacteremia as a complication of appendicitis, drug-induced vasculitis — summarized these topics and others in an on-line thread. Plus, one of the fellows shared an interesting paper on antibiotic-associated neutropenia. Much appreciated, Carlos!

Pace. Hospital census used to drop dramatically in the week before and after Christmas, leading to a delightfully slower pace in what is usually a very busy environment. While that effect is much less dramatic with the post-pandemic bed crunch, there are still fewer elective surgeries and admissions. So it’s still not quite as busy as during the rest of the year, a welcome break. And if you’re worried that I’m going to jinx this effect by even mentioning it, I refer you to a classic paper.

Diversity. Here’s a wonderful thing that made me smile on December 25, courtesy of Dr. Vamsi Aribindi:

Happy New Year, everyone!

December 22nd, 2023

A Holiday Season 2023 ID Link-o-Rama

Hey Image Creator, make a holiday greeting card in mid-century modern with dogs.

A bunch of ID (and a few non-ID) items of note as you prepare for the peak of the holiday season.

The President of IDSA has written an open letter to the American Board of Internal Medicine (ABIM) asking for changes to the recertification process. Current IDSA President Dr. Steven Schmitt proposes several modifications, all designed to reduce the burden and cost to the doctors. It importantly includes results from a member survey that shows a majority of ID docs believe the program “adds no clinical value, does not positively impact clinical practice and contributes to burnout.” A whopping 92% of early career ID doctors find the cost a burden. Note that it’s hard to find any survey that has responses so overwhelmingly negative about an ostensibly educational program.

Here’s part two of my commentary on this ABIM issue. In this update, the current president of ABIM gets mad, says something he later regrets (maybe), apologizes (accepted, thank you!), but sticks to his guns anyway. After reading this, my ID colleague/pal John Badley kindly sent me an email stating, “Paul, you and your blog are not despicable.” Thanks for the reassurance, John! And let me be clear once again — I do believe that it’s essential physicians continue to learn, and to keep their clinical practice updated, but I’m increasingly aware that the recertification process as currently designed has major limitations.

Patients who had recently used PrEP and acquired HIV were 7 times more likely to have baseline resistance at HIV diagnosis than those who never used it. The most likely explanation for this excess resistance is that PrEP was stopped, and then re-started after HIV was acquired. The most common mutation detected was M184V (lamivudine and emtricitabine resistance), so DTG and BIC-based three-drug therapy still should be active. Rather than use these data to discourage use of PrEP, we should leverage it to encourage better adherence and more regular follow-up.

Two investigational antivirals hastened time to recovery in people with COVID-19 compared to placebo. VV116 is a remdesivir oral analogue, and leritrelvir is a SARS-CoV-2 protease inhibitor given without ritonavir. Neither study reported significant safety concerns, and both would have fewer drug interactions than nirmatrelvir/r (Paxlovid), especially VV116. While the authors didn’t comment on rebound, recall that this issue does not happen with IV remdesivir. These two drugs (VV116 in particular) along with ensitrelvir all appear to have major advantages over our existing options for outpatients. As cases rise again this December (as they have every December since 2020), I eagerly — and confess impatiently — await better alternatives!

For children presenting to emergency departments with acute gastroenteritis, molecular testing led to a significant increase in identification of a potential pathogen and decreased the need for follow-up visits. The diagnostic yield increased from 3% in the pre-intervention period compared to a whopping 74% with molecular testing. Molecular testing was associated with a 21% reduction in the odds of any return visit, a clinical benefit strongly endorsed by my pediatrician wife (fewer “he had another loose poop” calls). These results remind me of one of the early studies of enterovirus PCR for meningitis, showing that even when you don’t have a treatment, sometimes just knowing the diagnosis can have benefits.

Treatment of men with UTIs and fever is one of the exceptions to the “shorter is better” rule of antibiotic courses. More relapses and treatment failures occurred after the 7 vs. 14 day course; strongly suspect prostate infection is the nidus for recurrence. I’d add high-risk vertebral osteomyelitis to this short list of conditions that may require longer treatment, based on both a prior observational study and anecdotal experience.

A microbiology laboratory tested 85 clinical isolates of beta streptococci for susceptibility to trimethoprim-sulfamethoxazole, clindamycin, and doxycycline. The surprise (to some) winner?  Trim-sulfa (100%), followed by clindamycin (85%), with every ID doc’s favorite doxycycline bringing up the rear, with only 57% susceptible. Some would argue that this in vitro activity of trim-sulfa vs. strep has long been proven in clinical studies of skin and soft tissue infections (such as one in kids and one in kids and adults), but that hasn’t stopped clinicians from frequently choosing double therapy with beta lactams plus trim sulfa for outpatient treatment of these infections. Guidelines, too, steer people away from trim sulfa for strep. Trim sulfa’s bad reputation vs. strep stems from an artifact introduced in a now outdated method of resistance testing, which had high thymidine content of the test media inhibiting the activity of the drug.

Weight gain after switching an NNRTI-based regimen to tenofovir DF/lamivudine/dolutegravir occurred only in those whose pre-switch NNRTI was efavirenz — not nevirapine. As previously observed, the women gained more weight than men. Also previously noted is that efavirenz has a weight-suppressive effect, which is not observed in other drugs in the NNRTI class — rilpivirine and doravirine also do not suppress weight. The mechanism by which efavirenz has this effect remains unclear, but I’m betting that this is an off-target toxicity. One confounder in this study is that most of the participants on NVP were on AZT/3TC, most on EFV were on TDF/3TC, and these NRTIs also influence weight.

In a placebo-controlled, randomized clinical trial, vitamin D did not lower the risk of upper respiratory tract infection in older adults. A large study, involving 16,000 participants, this is another negative vitamin D supplementation randomized trial we can add to a large pile. Oddly, in a prespecified analysis, the researchers observed a significantly lower occurrence of URI in the vitamin D group, compared to placebo, during summer only — exactly the opposite of what I’d expect. A protective effect also was seen in Black participants.

A synbiotic preparation called SIM01 improved certain symptoms of long COVID significantly more than placebo. These symptoms included fatigue, “general unwellness,” memory loss, gastrointestinal upset, and difficulty in concentration. There was a corresponding alteration in the treatment group’s gut microbiome. Confess I didn’t know what constituted “synbiotics” before this study — it means “a mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and activity of beneficial microorganisms in the gut.” And in case you’re counting, this is the third COVID-19-related randomized clinical trial coming from China I’ve chosen to highlight.

A graphic designer provided a detailed account of her devastating symptoms from long COVID. This is a long, quite heartbreaking piece, beautifully depicted, painful to read. Clinicians will appreciate that for some patients, the meticulous record keeping provides some solace, the sheer volume of it starting in 2020 no doubt correlating with the severity of her symptoms. She writes, “I thought that if I collected enough data, I would eventually figure out what was going wrong. But no matter how much data I collected or how many correlations I tried to draw, answers eluded me. Still, I couldn’t stop tracking. My spreadsheet was the only thing I could control in a life I no longer recognized.”

A detailed pharmacokinetics study evaluated bictegravir/FTC/TAF in 29 virologically suppressed pregnant women with HIV. The main findings were that while concentrations of all three drugs during the second and third trimester were lower than postpartum levels (roughly 40-80% of postpartum levels, biggest reduction for bictegravir), the mean bictegravir exposures were still more than 6.5-fold greater than the protein-adjusted 95% effective concentration. No virologic failure or infant transmissions occurred. This regimen — the most commonly used in the U.S. right now — is still listed as having “insufficient data” in pregnancy guidelines. I wonder if this small study will change that category.

Latent infection with Toxoplasma gondii was associated with increased mortality. Note that I wrote “associated” and not “causes”, as this large observational study found marked demographic differences between those who were seropositive and seronegative. One also wonders why the tests were sent to begin with — certainly it’s not a commonly ordered test, done only in very specific clinical circumstances. Nonetheless, it’s worth remembering that even latent infections can have consequences, as is increasingly evident with studies on CMV.

A Mostly Non-ID Section:

The story behind the “booming business” of cutting under a baby’s tongue to improve breastfeeding. Although well intentioned, this procedure has minimal evidence to support its now growing use despite being widely recommended by certain lactation specialists. It also takes advantage of parents during a time of great emotional vulnerability when there is already enormous pressure to breastfeed. Here’s what we do know:  it’s very profitable for the doctors and dentists doing the procedure, and it can have serious complications. I’ve been listening to wise pediatricians — especially one very close to me! — express concerns about this procedure for years, so it’s gratifying to see this exposed.

A survey of nearly 19,000 physicians found that nearly a third had a moderate or high “intention to leave” practice within 2 years. With the caveat that any survey may select only for those who are unhappy and want to express their discontent, the most striking figure from the paper places medical specialties in 4 different quadrants — along the vertical axis professional fulfillment, the horizontal proportion with burnout. Trust me, we don’t want to be in the bottom right (low professional fulfillment, high burnout). I was pleased to see that ID just escaped, sitting in the upper right — scoring higher than average on the burnout side of things (bad), but also higher on professional fulfillment (good)

A general internist wrote about the patients who fired him. In this excellent account of a difficult subject — and the valuable things he learned through the process — he tells the story of four such patients who left his practice. He concludes by writing:  “To keep this reflection under 2000 words, I leave out the stories of two other patients. I am also not sure I could have tolerated writing more.” We need more of these stories in clinical medicine to balance out the “I came in and saved the day” anecdotes — which not surprisingly are much more common!

Hey, happy holidays everyone! Let’s wrap up the year with these American-born dancers living in Galway performing to a song written and performed by a singer-guitarist from Puerto Rico, who quite amazingly was born blind and started playing the guitar at age nine.

December 8th, 2023

Clinician-to-Clinician Advice Is Great for Everyone but Still Horribly Undervalued

One of the best things about being an ID doctor is that you get to interact with all the medical and surgical specialties. This is one of the most common answers to the question, “Why did you choose to specialize in ID?” and it certainly resonates with me.

As a result, we’re frequently in the position of providing clinician-to-clinician advice — which, when done without seeing the patient, was historically called a “curbside” consult. Informally asked, often prefaced with “Can I ask you a quick question,?” these curbsides have pros and cons that I’ve written about on this site numerous times.

It’s a topic near and dear to my heart, so much so that I have an entire talk on this subject that starts with several slides outlining both the benefits and the risks of this practice. And for the hard-liners (see photo above on the right) who never do clinician-to-clinician advice without seeing the patient, trust me there are benefits, some of which I’ve summarized on this slide from my talk:

In a similar theme, around 10 years ago, our hospital system started offering “eConsults,” adapting similar programs from elsewhere. Instead of referring a patient for in-person consultation to a specialist, clinicians could place an order in the medical record, and a specialist would review the question, the data from the patient’s chart, and write a note.

This form of consultation occupies an intermediate place between actually seeing, interviewing, and examining a patient, and the informal “curbside” consults where you give just general advice, undocumented anywhere. Completing the note is expected within 24 hours. Because eConsults are asynchronous, meaning we specialists don’t need to respond immediately, they are far less disruptive than getting paged or called directly.

A huge advantage of this approach over curbsides is that we can review the primary data. In addition, the consulting clinician now has specific advice documented in the chart on how to proceed, which may include ordering additional tests or modifying treatment. In a small proportion of eConsults, we advise that the clinical scenario is too complex to resolve without a formal visit. After all, we can’t put a limit on the complexity of the case — that’s at the discretion of the consulting clinician. When that happens, fortunately, we’ve still been able to weigh in on tests to order ahead of time that will make an in-person visit with us or another specialist more valuable.

How has the program done?

To say eConsults have caught on vastly understates it — they are a huge hit. Imagine if a miraculous Beatles reunion became the opening act for Taylor Swift. To quote one primary care doctor who previously had a solo practice, “It’s by far the best thing about working here.”

You can easily see why they’re so popular. Not only do clinicians get access to nearly the full range of medical and surgical expertise at our academic medical center, often an eConsult can spare their patients the inconvenience and cost of an extra doctor visit. Indeed, published data on our program strongly show that eConsults decrease the volume of formal referrals, while increasing their appropriateness. Evaluations from different centers (here and here) had similar findings. Implied in these data is that care efficiency improves and the total cost to the healthcare system declines (fewer visits = lower costs).

Sounds like these eConsults are a real advance, for patients, clinicians, and payers, a rare win-win-win trifecta — so much so that we proposed expanding the eConsult service to inpatients to deal with the never-ending deluge of curbsides that arise in hospitalized patients.

So far, all sunshine and warm tropical breezes. So, what’s the problem?

No one has figured out how to pay for these things.

In a healthcare system where procedures dominate the payment landscape — the more, the better! — an advance in efficient patient care just can’t get the attention of the payers or the administrators holding the purse strings. Yes, there are billing codes for clinician advice activities without seeing the patient, but the net pay is poor (average 0.5-1 RVU, latest conversion factor $33.06/RVU), and the technical hurdles of getting reimbursement can be tricky to implement. Plus there’s this requirement:

THESE REQUIRE INFORMED PATIENT CONSENT! Since the consulting physician is not seeing the patient, the requesting physician must obtain and document informed consent.

And guess what? If you or another ID doctor ends up having to see the patient and do a consult on the case within a week, that “formal” consult can’t be billed! As a result, hardly anyone uses these codes, at least based on my emailing a variety of ID doctors in academic medical centers, and by the lukewarm responses to an online query.

So if we’re not billing insurance, how do eConsults get supported? Note I’ve used the common euphemism for money — support.

Here, our hospital system pays us for eConsults out of the Physicians’ Organization budget, a finite resource; they set the reimbursement at $50/eConsult when we started, an amount that hasn’t budged despite a substantial increase in the cost of living over the last decade. In addition, they declined our offer to expand eConsults for inpatients, even though we offered to expedite these to make discharges more efficient.

I queried a bunch of other ID doctors in a variety of practice settings about their payment models, and their responses were diverse (and fascinating). Some get paid a set amount, like our program. One does use the “interprofessional consults code” and makes do (unhappily) with the meager payments. Another uses these codes, but augments them to what seem to me to be much more reasonable rates:

(For the record, in my experience, most eConsults would be in the third or fourth category, occasionally fifth if they involve contacting the consulting clinician or a reference laboratory.)

The ID director at a “closed” healthcare system says they have no specific payment for eConsults, but that they are tied directly to the ID doctor’s job responsibility. He estimated that “all clinician-to-clinician advice for the on-call ID doctor, without direct patient contact, accounts for 3–5 hours/day” — a substantial time commitment! Finally, Dr. Allison Nazinitzky, who does ID locums work, shared with me that one of her telehealth contracts pays her $125 for an “interprofessional consult with note — a flat fee no matter how long.”

(Check out my interview with Dr. Nazinitzky. Her experience finding the true value of ID clinical care is dynamite.)

The medicolegal aspects of eConsults should be factored into any estimation of the value of the program. eConsults may reduce medicolegal risk for the referring clinician, but they substantially increase it for the specialist taking it on. Why? As noted in an excellent review of the legal risks of curbside consults, this is because we are now explicitly reviewing the patient’s chart and providing specific advice:

The closer a physician gets to providing very specific information—what dose to start with, when to draw labs and what other kinds of studies to get, and what to do specifically with a particular patient—the closer that physician is coming to being part of the care team, as opposed to just providing general information.

Despite the boilerplate language we insert at the end of each note indicating the limitations of eConsults, this will serve as little protection if a suit is filed. As part of the care team, our names can be included in any filed suit. And even if we are later dropped because we never saw the patient, the process itself can be long and painful.

So what’s the solution? I say include these advice services as part of what constitutes the job of a clinical ID doctor — give us appropriate RVU credit and/or payment for it — and make it commensurate with the time, value, and medicolegal risk associated with the service.

And if that doesn’t happen, let’s do what Dr. Andrew Pavia recommends, in my response to the query about whether he uses the interprofessional consults codes:

In other words, stop doing eConsults until they’re properly supported. Seems like a good plan!

November 23rd, 2023

Giving Thanks — This Time to You, Readers of This Thing

Louie with his favorite dessert plates

Most years around this time I post some ID-related things to be grateful for — a research advance, a nice shift in epidemiology showing fewer people are sick and more are living longer, a new drug approval we’ve been eagerly awaiting. That kind of thing.

Last year, for example, it was gratitude that mpox had come under control (fingers crossed). That dolutegravir and bictegravir were holding up just fine. That Covid-19 finally seemed to be trending toward true endemicity (second pair of fingers crossed). And a quick comment about a certain social media site that remained a “wonderful and entertaining place to learn”, chaos at the top notwithstanding (yeesh, still holding out hope).

This year, I’m doing something different.

I’m going to thank you, whoever’s out there reading this thing, for sticking with it all these years. I’m truly grateful for your emails, your comments, your feedback, our chats at professional meetings, but most especially, for your eyes just reading this. Face it, if no one were reading these posts, I highly doubt the fine people at NEJM Journal Watch would continue supporting it. So thank you so much, and keep reading!

(Actually, if no one were reading it, I’d probably be writing something somewhere anyway — that’s how I’m wired — but you know what I mean.)

At this year’s IDWeek, at the Medical Education Community of Practice meeting, I met Dr. Priya Kodiyanplakkal, an ID doctor from New York. In the pre-meeting chat, she gave me the greatest compliment I could imagine about this blog, one she later kindly posted in this convention center lobby photo:

What she said is exactly what I’m trying to do — to convey what it’s like practicing clinical ID, the “everyday realities of being an ID physician” for all of us out there doing it.

And while I can’t know exactly who the readers are, I know from the numbers that it’s not just ID docs — it’s a much larger group of healthcare providers, people who find ID interesting, or enjoy my takes on broader issues of clinical practice (e.g., rants against fax machines, ABIM recertification, CME requirements), or just want to see the latest photo of Louie.

(My wife Carolyn purchased those dessert plates from a store which had them on sale in a remainder bin. Can you believe it?)

But whoever you are, I do know that we’ve built a remarkably nice, smart, and civil community. At one of our editor’s excellent suggestions, we have a moderated comments section, meaning we review the comments before posting. With few exceptions most of them are thoughtful and not at all nasty — it’s uncommon that we have to ding one for breaking the site’s rules. A rarity for internet communication!

Speaking of the editors, thank you also to the three of them, who take turns reviewing each post before it appears, scanning for typos, unclear prose, and unauthorized material. They’ll probably not be happy with me that this one went up without their approval, but this is a national holiday, after all — don’t want to bother them. Plus, I can guarantee that I hold all the rights to that photo at the top.

So after starting writing here in 2008, and 877 posts later, I’m still at it — thanks to all of you readers.

Hey — you can still buy these plates on eBay, in case you’re wondering. Happy Thanksgiving, everyone!

November 16th, 2023

Being a Good Doctor — Why Are the Simple Things So Hard?

The simple things that make someone not just a doctor — but a good doctor — can slip away from us when we’re too busy, or tired, or preoccupied, or hungry. That’s why it’s wise periodically to be reminded of the “soft skills” that, while individually not tricky, together make a huge difference in how patients perceive us.

“Soft skills,” by the way, is the term coined recently by Dr. Robert Oubre, a hospitalist from Louisiana who specializes in Clinical Documentation Improvement, or CDI. Periodically imparting his wisdom on social media and in his newsletter, he recently posted something entitled, “Preventing and Protecting Against Lawsuits.” Here’s what one lawyer told him was a critical part of avoiding legal trouble during patient care:

You should practice in a way that causes your patients, and everyone you work with, to like you.

Be likable! How sensible. Because beyond lawsuit protection, I’d argue these soft skill make up critical components of patient care, and legal risk-reduction is just a corollary benefit.

Here are some of those skills he cites, in bold, followed by my comments — it’s a great list. He writes from the perspective of hospital care, but a lot of them transfer over to the clinic.

Sit. In the hospital, patients are often in bed, sometimes in a chair, but hardly ever standing. Get on their level. This small physical act greatly increases their sense that you care about them and that you’re giving them time. Logistically, it’s not always easy — family might be visiting, chairs might be occupied or have stuff on them, the room might be architecturally challenging. But try to make it happen when you can.

Call. Find out who they’ve listed as their designated family member or friend to help out, and keep that person updated. We had the importance of this action driven home to us during the dark days of the pandemic, when families couldn’t visit. One time-saving strategy is to have the patient call while you’re rounding in the room or during the office visit, and put their family member on speaker phone.

Ask, “What questions do you have?” rather than “Do you have any questions?” The former invites questions, the latter subtly discourages them.

Introduce yourself. Patients meet a ton of clinicians during their hospitalization, especially if it’s a long and complex one. Coverage changes, weekends and holidays happen, specialists aplenty get called in. For many services, the era of working extended blocks of time of consecutive days is long gone. So it never hurts to remind patients who you are — and do it repeatedly, as with rare exceptions, we are terrible with names. (You lucky few out there who are good with names are fortunate indeed!) During his wife’s recent care, Dr. Oubre posted the following — that empty, confused feeling when people fail to introduce themselves:

Use the patient’s name. There’s really no excuse for not greeting the patient by their name — after all, we all know it, it’s right at the top of the medical record. So use it — “Good morning, Mr. Smith”, “Hello again, Ms. Lopez”, “Hi, Mr. Gupta, how was your night?”, etc. (Then introduce yourself — again. See above.) If the name is unfamiliar or hard to pronounce, ask them how to pronounce it, and do your best to get it right. Plus, on those occasions when a patient changes rooms, this action provides another check that you’re not about to take a history, do a physical exam, or worst of all, do a procedure on the wrong person. (Yes, it happens.)

Acknowledge others in the room — and find out who they are. I added that last bit. Both are crucial. Let’s imagine you walk in the room, and your patient (a man) is accompanied by a woman. Try this script: “Hello Mr. White, I’m Dr. Schwartz, nice to meet you.” Turn now to the woman, and say, “And who do we have with us today?” Not — “… and is this your wife?” Most of the time it will be the spouse or partner — but not always. Everyone has made the mistake of assuming it’s a spouse, only to find out it’s the patient’s friend, or sibling, or parole officer, or daughter (ugh), or mother (ugh again). If you haven’t yet made this embarrassing generational error, learn from our mistakes and don’t do it yourself.

Corollary to this point: On rare occasions, your patient doesn’t want the extra person there, but has been forced (or even bullied) into it. Give them an opportunity to be alone with you, by asking if they’d like the person to be there during the history or during the physical exam. For young adults (ages 18-25, give or take), I typically allow the parents in the room during the initial history, then ask them to leave during the physical at which time I can ask more delicate and private questions.

American Theater Poster, 1899

Mention the NAME of other doctors that are caring for them. While you may not be able to do this for all the doctors, try at least to name the primary attending physician, or in the outpatient setting, the referring clinician. And don’t just mention their name — tell them you’ve been communicating. “I heard from Dr. Li, your primary care doctor, that you had a positive TB blood test and had some questions”, or “I know from reviewing your chart that Dr. Aslam thinks you might need a change in antibiotics.” With so many people involved in a patient’s care, it’s critical to inform them that everyone is working as a team to help them get better — “Establish a team-work mentality” is another one of Dr. Oubre’s soft skills, and this strategy affirms this team work.

Smile. Listen. Affirm their experiences. One patient I saw with severe asthma told me how grateful she felt when one of our gifted pulmonologists said something like, “That must be very scary for you” when she described the sensation of having an asthma attack. Remarkably, in all the years of seeing various clinicians, no one had ever mentioned that before. Having this doctor acknowledge her fear went a long way to establishing their very successful long-term care plan.

For our new HIV diagnoses, we make sure to acknowledge the feelings they have when they find out their HIV test returned positive — something along the lines of, “It can be hard to hear that the test is positive.” Then pause, and let them speak. We can then quickly move on to reassure them that the diagnosis is no longer a death sentence, that treatment can lead to a long and normal life, and that we’ll help them adjust to this new reality of having a chronic (but treatable!) condition.

Follow up on promises. My wonderful (and still dearly missed) late colleague Paul Farmer took this to heart more than anyone I’ve met. No matter how busy or crazy his schedule, if he told a patient he’d be back to hear more of their story, or to give them boots, he’d do it. (Here’s the boots story, #2 in the list.) I’m not saying we need to buy everyone boots — but his actions stand out as a good model for what we should aim for.

Be approachable to nurses. This statement, of course, applies to all the members of the care team. There’s no room in good patient care for outdated hierarchies or authoritarian actions. The nurses, social workers, pharmacists, front desk staff, the person delivering the food tray, transport personnel — we’re all there to accomplish the same thing, which is to get our patients better. The more we acknowledge and validate the others we work with, the better we’ll do.

Remember to look at them — not just the computer. Sure, we can consult the electronic medical record during the visit — just tell them that’s what you’re doing, and even apologize if you need to go on a lengthy search. Or invite them over to do it with you! But staring exclusively at the computer screen and typing while seeing a patient is a surefire way to create distance between “us” and “them.” And yes, I added this one to the list, as it’s long been a pet peeve of mine.

A non-medical person reading the above might think this stuff is easy. What’s the big deal? But trust me, the fact they seem so obvious stands in sharp contrast to just how difficult they are to do consistently, in particular when external demands weigh in as distractions.

But try we must — not only to avoid lawsuits (the original purpose of Dr. Oubre’s excellent list), but just to be a kind and caring doctor.

Anything left out you want to mention?

It certainly never hurts to ask about pets — people love talking about their pets, especially if they have a special talent.

October 31st, 2023

HIV Research Highlights from IDWeek 2023

Having already featured an important non-HIV clinical research study from IDWeek — the amazing ACORN trial — I turn now to a grab bag of HIV-related studies, a veritable Halloween treat bag full of them.

(Note to self: What’s with that “Halloween treat bag” reference? Couldn’t you come up with a less awkward way to link this content with the posting date?)

Note acknowledged. I’ll think of something snappier for next year!

Here are the studies:

Compared to placebo, semaglutide markedly reduced weight and total body fat in PWH with lipohypertrophy (#1984). Interestingly, there was no effect on ectopic fat in the liver and pericardium, locations which correlate with some adverse outcomes. Lead investigator Grace McComsey (who has led several remarkable single-center studies on metabolic issues) cautioned that lipoatrophy might worsen with this treatment, potentially a concern in particular for our older patients who received thymidine analogue drugs (ZDV, d4T) in the distant past.

In a large (n=225) retrospective cohort study, GLP-1 receptor agonists were more likely to lead to > 5% weight loss in those with higher baseline BMI and longer duration of treatment (#1983). Dulaglutide appeared less likely to achieve this weight loss than semaglutide and terzepatide. What does it say about the current state of outpatient HIV management that these two studies of GLP-1 agonists were featured oral abstracts at an ID meeting?

One dose of penicillin is as good as three for early syphilis (#2889). During my ID fellowship, a local expert strongly opined that 3 doses were necessary, especially with concomitant HIV. Not so say the results from this multicenter randomized trial, where response rates were comparable with 1 vs 3 doses, including in the 67% of study participants who also had HIV. Data confirm what is recommended in treatment guidelines.

A bunch of studies looked at various comparisons between BIC/FTC/TAF and DTG/3TC, two highly popular and effective regimens. In an interim analysis of a randomized clinical trial comparing remaining on BIC/FTC/TAF vs. switching to DTG/3TC, the switch strategy was non-inferior at week 24 (#1603). There were more discontinuations in the DTG/3TC arm, explained in part by the open-label nature of the study (ascertainment bias). As with the TANGO and SALSA switch studies, switching to DTG/3TC did not result in weight loss. Interestingly, a person who remained on BIC/FTC/TAF experienced virologic failure at week 12, with detection of M184V and G140S mutations. I believe this is the first report from a prospective study of any participant experiencing virologic failure with INSTI resistance on this regimen — wonder if there was prior treatment failure on RAL or EVG.

Switching to BIC/FTC/TAF (n=3527) or DTG/3TC (n= 2213) in clinical practice maintained virologic suppression, with very rare instances of virologic failure (#1023).  Only two and three cases of virologic failure occurred, respectively, after over a year of follow-up. Since this is a non-randomized study, the patient characteristics differed between those getting BIC/FTC/TAF vs. DTG/3TC: BIC/FTC/TAF recipients were significantly more likely to be Black, on government insurance, have experienced prior virologic failure, and have a lower CD4 count; those on DTG/3TC had a lower eGFR. Regimen discontinuation occurred statistically earlier with DTG/3TC versus BIC/FTC/TAF.

Related to the above, clinicians gave different reasons for switching to BIC/FTC/TAF vs. DTG/3TC (#1570). For BIC/FTC/TAF, these reasons were inconsistent healthcare visit attendance, adherence challenges, substance use, HBV coinfection, or viremic on current regimens. For DTG/3TC, concerns about low eGFR or excess weight gain motivated the switch. For the weight issue, note that none of the switch studies of DTG/3TC have shown any difference between BIC/FTC/TAF and DTG/3TC when it comes to weight — and IDWeek provided another one (see #1603 above).

Out of 1843 PWH who started CAB/RPV in a US-based cohort, 229 (12%) had a detectable viral load at treatment onset, a strategy outside of licensed indications (#1028). For 93 of them, the viral load was > 200, so true virologic failure. Virologic suppression was achieved in 82% overall, with 4% experiencing virologic failure. There was scant data on pre- or post-treatment resistance, or more importantly why the clinicians chose this regimen — especially since the median CD4-cell count was around 500! As noted previously, I strongly believe that if we’re using this treatment for virologic failure, we should limit it to those with low CD4-cell counts at very high risk for disease progression.

Data from a claims database suggests that adherence and persistence on injectable CAB/RPV is better than oral ART (#1024). Adherence was generally high for both strategies, but significantly higher with CAB/RPV using the 90% adherence threshold. Data are both reassuring and perhaps not surprising, given that CAB/RPV requires fewer doses, our generally careful selection of candidates for this strategy, and the intense efforts to keep those who are on it engaged.

In a pilot study, 33 patients successfully received CAB/RPV at home (#1027). Remarkably, a single nurse drove to homes in a 3000 square mile region. The study sent the medications by mail, with instructions for home refrigerator storage and pre-visit preparation by the patients. This is a good proof-of-concept study, but for obvious reasons not sustainable by most healthcare systems. And while I once thought that pharmacies would be a good location for getting CAB/RPV, the commercial pharmacies in our region are now massively understaffed and overwhelmed.

In a prospective cohort study, women with low-level viremia had higher rates of treatment failure, with a trend toward more multi-morbidity (#1025). These results are similar to those observed in cohorts made up of mostly men. Management strategies are still uncertain, aside from redoubling efforts at ensuring adherence and using high resistance barrier regimens.

In large sample of MSM PWH engaged in care at academic HIV clinics with a program for anal cancer screening, only half ever received any screening (#1478). Follow-up was notably low as well. Test performance of the screening anal pap was poor — there were high rates of “unsatisfactory” results, and low rates of detection of high-grade lesions. In other words, the anal pap falls far short of required sensitivity and specificity to be a good cancer screening tool.  Controversial opinion — we should stop doing anal pap smears until we have a better screening test, and in the meantime figure out which MSM with HIV should be referred directly to high-resolution anoscopy.

Hepatitis B reactivation in PWH who have isolated hepatitis B core antibody and switched to non-hepatitis B-active ART is uncommon, but does occur (#1026). These regimens lack any of tenofovir, lamivudine, or emtricitabine. Data came from a large VA cohort study, in which 5,954 were deemed at risk, and 89 (1.5%) experienced reactivation (turning surface antigen positive or having detectable HBV DNA). It’s less likely if surface antibody is also present, and much more likely if they were historically surface antigen positive (20% risk). Studies such as this one become much more clinically relevant in the CAB/RPV era.

In a cohort of PWH at an academic medical center, 23% of those with cirrhosis died during a 3-year follow-up period (#1983). This was 4 times higher than the overall HIV cohort mortality and occurred even though 90% had HIV viral suppression. Although HCV was the most common cause of cirrhosis, the study did not include details on HCV treatment history.

We’ve got PrEP, and PEP, why not PIP (“PEP in Pocket”, #2894)? In this study, 112 people at risk for HIV but with infrequent exposures were provided with 28 days of DTG plus TDF/FTC in case such an exposure occurred. Strategy allows for self-administered prevention and follow-up, a choice made by 35 of the participants, with high rates of follow-up. Some transitioning to PrEP.

That’s a wrap! Am sure I missed something interesting, as IDWeek now has a good portfolio of research studies, in addition to the great lectures, debates, and overall schmoozing.

Speaking of research, I submit the following video of a really fun research job.

October 17th, 2023

A Brilliant Strategy for Conducting Clinical Trials — The ACORN Study

Hey Bing AI, make a cartoon battle between cefepime and pip-tazo.

The secret to doing a great clinical trial is quite simple. Here, I’ll share it with you:

  1. Come up with an important clinical question for which there’s true equipoise.
  2. Choose primary and secondary endpoints that people care about.
  3. Make the inclusion and exclusion criteria easy to understand and chosen so that they define a readily available and broadly applicable study population.
  4. Create a system in which referrals, enrollment, and informed consent are as frictionless as possible.
  5. Start the study, and collect the baseline and follow-up data.
  6. Analyze and report the results.

There, piece of cake! Off you go, time to get started.

I hope your sarcasm meter is turned on because pulling off any of the above is in fact exceedingly difficult. That’s why the ACORN study comparing cefepime with piperacillin-tazobactam (pip-tazo) — presented last week at IDWeek, and simultaneously published in JAMA — is so wonderful. And it’s not just because of its clever name:  Effect of Antibiotic Choice On ReNal Outcomes.

Let’s go through the above recipe and see how they did.

Come up with an important clinical question for which there’s true equipoise. In adults hospitalized with acute infection, which antibiotic is better: cefepime or pip-tazo? Members of Team Cefepime would cite pip-tazo’s notorious association with kidney injury, especially when combined with vancomycin, and the broad anaerobe coverage, which may further disturb the microbiome.

Team Pip-Tazo would counter by reminding Team Cefepime about their drug’s neurotoxicity and say that pip-tazo’s nephrotoxicity may be artifactual — the result of inhibiting tubular secretion of creatinine, with no change in actual glomerular filtration rate (GFR) based on cystatin C measurements. Plus, Team Pip-Tazo will defend that extra anaerobic (and enterococcal) coverage as helpful for empiric therapy.

(Brief shout-out to Team Neither, made up of antibiotic stewards arguing that empiric coverage of Pseudomonas is not needed for all acutely ill people. You’re welcome.)

Choose primary and secondary endpoints that people care about. From the paper’s quick summary:

Does the choice between cefepime and piperacillin-tazobactam affect the risks of acute kidney injury or neurological dysfunction in adults hospitalized with acute infection?

That’s pretty clear. After all, the broad-spectrum coverage of these two drugs is similar, so adverse events are likely to dictate the best choice. If the study finds differences in efficacy, that would be quite interesting as secondary or exploratory endpoints. But common sense dictates that they’re probably not that different in efficacy, so setting the study up as a superiority trial on efficacy (“powering” for an endpoint of days of ICU care or death) would require a sample size so large as to make the study impractical.

Make the inclusion and exclusion criteria easy to understand, and chosen so that they define a readily available and broadly applicable study population. How about anyone in the emergency room or medical ICU for whom a clinician plans to start one of these two antibiotics? That’s pretty simple — and it must happen a zillion times a day in hospitals all over the world.

Create a system in which referrals, enrollment, and informed consent are as frictionless as possible. Here’s the true genius of the ACORN trial. After the doctor ordered either cefepime or pip-tazo in their medical center, the investigators leveraged the electronic medical record to screen automatically for critical exclusion criteria. With none found, their order triggered a prompt for the doctor to consider enrolling the patient in the trial.

During primary investigator Dr. Edward Qian’s excellent presentation at IDWeek, his slide with the image of the prompt (available on the study’s supplemental appendix) elicited gasps of amazement — at least it did from clinical trials geeks like me. This is just a brilliant way to encourage referral and enrollment. Frictionless clinical research at its best!

(Brief aside: I’m not sure about your hospital, but where I work, changes to EPIC, our electronic medical record, move forward about as fast as that slug you found under your garden’s flowerpot. What was this wizardry Dr. Qian and colleagues did to scoot this slug along?)

But what about informed consent? As discussed in detail on page 10 of the study’s appendix, it turns out informed consent to a study can be waived if a study is deemed minimal risk and the intervention is an emergency. Empiric cefepime or pip-tazo for acutely ill, hospitalized febrile adults certainly meets the criteria of standard of care (minimal risk), and the sooner antibiotics start the better (emergency). Check and check!

Start the study, and collect the baseline and follow-up data. From November 10, 2021 to October 7, 2022, 2634 participants enrolled in the study at a single center. (I told you this happens a zillion times a day — full enrollment in less than a year from just one hospital!) Patients enrolled were well-matched at baseline, with sepsis the initial diagnosis in just over half. The median duration of the initially assigned antibiotic was 3 days, but a substantial fraction received treatment for longer.

Clinicians added vancomycin in 83% of the cefepime group and 81% of the piperacillin-tazobactam group for a median of 2 days. Roughly equal proportions of both study arms had treatment modified via other antibiotic changes, including switching to the other drug (cefepime to pip-tazo in 19%, pip-tazo to cefepime in 17%), or broadening treatment by adding an aminoglycoside or switching to a carbapenem. In other words, the very common practice of antibiotic switches for critically ill patients — don’t just stand there, start meropenem! — was equally common in both arms.

Analyze and report the final results. For the primary endpoint, the highest stage of acute kidney injury or death by day 14 did not significantly differ between the cefepime group and the pip-tazo group. Even the addition of vancomycin didn’t have a differential effect. However, for the important secondary endpoint of delirium or coma, here the pip-tazo group had significantly fewer hospital days with this complication. Deaths were similar between arms, as were a bunch of other clinical and laboratory endpoints.

So Team Pip-Tazo wins, though it’s a really close call. And may the pip-tazo/vancomycin nephrotoxicity RIP, at least based on this short-term exposure.

Now no study is perfect, and the authors responsibly address the limitations in their discussion. For me, the biggest one is that as an open-label study, clinicians may have been more prone to make the diagnosis of encephalopathy with cefepime, and this turned out to be the only significant difference between the two strategies. Read the full paper and the accompanying editorial to see further discussion.

Limitations notwithstanding, the study remains an impressive feat of generating clinically relevant evidence on an important topic, and doing so quickly in a way that harmonizes with actual patient care. The novel strategy of enrolling eligible participants through the electronic medical record in such a seamless way is a model for other clinical questions in both ID and beyond.

What should we study next?

Because it can’t be as hard as doing these things on a treadmill …

October 8th, 2023

An October ID (and Non-ID) Link-o-Rama

The Lyme Laser.

For those venturing next week to IDWeek here in Boston, fall gives us our very best weather. Comfortable sunny days with brilliant blue skies, cool evenings, low humidity — great weather for exercising and sleeping. Usually you just need a light jacket. And now, after one of the rainiest Septembers on record (boo!), October has so far has been heavenly (yay!).

But you don’t come to this site for a New England weather report, which might change day-by-day anyway.

Let’s go to the links, starting with ID topics:

  • Lyme vaccine clinical trials continue, and one candidate is quite far along. Fingers crossed, at least one of these two vaccines will be safe and effective, then widely adopted in highly endemic areas. My non-medical friends here frequently wonder why there is no vaccine for humans if their dogs can get one. I tell them there was one — but it got caught up in the controversial cloud that follows this disease around like dust over Pigpen.
  • How’s this for an example of this dust? Or crap, to be more accurate: You can get treatment with a “Lyme Laser”. It “addresses the concern of the biofilm established in the advanced stages of Lyme disease,” and “enhances the body’s natural abilities to improve function and regeneration.” Seriously, the unvalidated and potentially dangerous “treatments” offered for this serious infection continue to strain imagination. Note that pricing on this site (and others just like it) is conspicuously absent.
  • The NIH-sponsored clinical trial ACTIV6 for COVID-19 is still open, evaluating metformin. The study will (I hope) confirm the benefits seen in the COVID-OUT trial, in which metformin reduced the incidence of long COVID by 41%. Importantly, people can also take other COVID-19 treatments and still participate. I’m particularly interested to see if it can reduce the incidence of rebound after nirmatrelvir/r, which remains a bedeviling problem.
  • PEPFAR may be in trouble. Could a rare example of bipartisan political support for a hugely successful public health program come to an end? That’s the worrisome message expressed in recent coverage of PEPFAR, which pays for HIV treatment in resource-constrained countries with high HIV prevalence, especially in Africa. At last estimates, the program has saved 25 million lives. Wow.
  • The CDC called for comments on the use of doxycycline for post-exposure prophylaxis for STI prevention. You will not find them by clicking this link, and getting to them is tricky, so here are “guidelines” on how to find the draft guidelines: Go this YouTube video, watch the summary of the evidence, and eventually (at 15:15) you’ll reach this:
  • In related news, this modeling study shows that adopting doxycycline for STI PEP using these criteria would be an efficient use of resources. Monitoring for STI resistance will be critical.
  • Can oral swabs run on a multiplex PCR platform help diagnose community acquired pneumonia? In this study, correlation between oral and lower respiratory results was high when S. pneumoniae and H. influenzae were the cause of the pneumonia. Sure would be easier than trying to get an induced sputum.
  • Ceftobiprole was noninferior to daptomycin in treatment of Staph aureus bacteremia. Wow, talk about a blast from the past — I thought this cephalosporin (with activity against MRSA) had long been abandoned, but here it is again! Look for this paper in many ID and medicine journal clubs over the next few months, as there are numerous questions about the study design and the clinical implications. I worry in particular about the control arm — daptomycin (not oxacillin or cefazolin) for MSSA (76% of study participants)? And was daptomycin underdosed?
  • In other MSSA bacteremia research, here’s a different prospective randomized clinical trial: The study compared cloxacillin alone vs. cloxacillin plus fosfomycin. The combination regimen failed to show superiority, despite more rapid clearance of bacteremia at day 3 — reminds me of adjunctive gentamicin in this regard. Great to see these studies of Staph aureus bacteremia, which is almost certainly the most common reason for inpatient ID consults, at least in the United States.
  • Herpes simplex encephalitis has a high rate of subsequent neurologic complications, with immune-mediated choreoathetosis particularly common. This in-depth study suggests corticosteroid treatment of this late complication is warranted. And it’s a reminder that despite being “treatable” with high dose intravenous acyclovir, HSV encephalitis remains a devastating diagnosis — patients and their families should be counseled up front about the potentially serious outcomes.
  • The viral dynamics of COVID-19 have dramatically changed in relation to symptom onset since the start of the pandemic. Viral loads of SARS-CoV-2 now peak at day 4 of symptoms (not at or right before symptoms start), with rapid antigen testing gradually increasing in sensitivity over symptom-days 1-4. The results clearly emphasize the need to re-test in patients with negative tests early in the illness, and also have infection control implications. Our broad pre-existing immunity is responsible for this “new normal”.
  • The WHO endorsed use of a highly effective malaria vaccine, the second vaccine now available. Work on malaria vaccines has been a struggle for decades, so this progress is a welcome advance indeed — because in separate news, the mosquitoes appear to be winning. Global malaria deaths are ticking up, and other mosquito-borne diseases such as dengue and chikungunya continue to spread.
  • These authors provide an interesting perspective on those annoying low-level viral load results that create all kinds of anxiety — namely, that the labs and clinicians should focus on the 200 copies/mL threshold as the important one for “U=U,” as this was the lowest threshold used in the large studies evaluating HIV viral load and transmission. While I agree that this is a reasonable approach (and the one I use in clinic), there is some uncertainty around this threshold, since most of the people in these studies of transmission on ART had undetectable viral loads — the 50-200 sample was necessarily small. Nonetheless, I 100% agree that flagging these results with a big red exclamation point is unnecessary. And check out panel 4 in the figure.
  • The Nobel Prize in Medicine went to Katalin Karikó and Drew Weissman, whose work led to the development of mRNA vaccines against COVID-19. Lots of chatter about how Karikó “failed” in traditional academic research, which prompted her to leave her university lab setting because she was unable to get grant support. Let’s face it, the weeding out process in academic medicine specifically and science in general will definitely overlook some innovative geniuses, as grant-review committees are famously conservative in favor of established researchers and familiar strategies.
  • You know that strange sensation of time distortion since the start of the COVID-19 pandemic? “Pandemic skip” is a great descriptive term. And though the writer of this piece is just 30, it applies to every age, doesn’t it? And sometimes it feels like just a few months since those terrible dark days in 2020, and at other times it feels like it must have been many, MANY years ago, certainly much more than just 3. Don’t you agree?
  • Here’s a poetic rumination on microbial odors. Impressive alliteration on display: “From the fungal fragrances that sing of environmental mold to the bacterial bouquet that warns us off week-old leftovers, our air comprises a microbial miasma of information, ripe for research and exploration.” I’m sure Cliff, the C. diff-sniffing dog, would agree!

Now, a brief non-ID section:

Since people will be coming from all over the world to IDWeek, how about this impressive and nimble take on country-specific accents? Wow, what talent. What’s your favorite?

Hope to see many of you at IDWeek!

September 22nd, 2023

Long-Acting Cabotegravir-Rilpivirine for People Not Taking Oral Therapy — Time to Modify Treatment Guidelines?

Cephalopods, by Jean Baptiste Vérany.

HIV treatment guidelines are understandably reluctant to endorse practices that have limited data. Having served on two such panels (previously, DHHS and currently, the IAS-USA guidelines), I totally get this — you don’t want to put a stamp of approval on strategies that may ultimately do more harm than good.

With the caveat that I cannot speak for the guidelines panel I currently serve on, I can give you my opinion on a topic much discussed among us ID and HIV specialists — namely, the use of long-acting cabotegravir and rilpivirine in people not taking standard oral ART, despite all our efforts to encourage them to do so.

Here it is:

If the alternative is untreated and progressive HIV disease, and the patient has advanced immunosuppression, we should stop discouraging use of this potentially life-saving therapy.

I base this on what are now a few published studies, including the original reports from UCSF, a follow-up from them with a larger sample size, a modeling analysis demonstrating substantial projected survival benefits, and now — just published in Clinical Infectious Diseases — a small case series from a different clinic with comparably excellent outcomes.

At a Ryan White-funded HIV clinic at the University of Mississippi Medical Center in Jackson, clinicians began offering injectable CAB/RPV in February 2022 as a salvage option to people with HIV (PWH) who had viremia despite intensive case management strategies. Since that time, they have offered it to 12 patients — 7 women, 5 men. The baseline mean CD4-cell count was 233, and HIV viral load 152,657 copies/mL, with 5 of 12 having a history of AIDS-defining opportunistic infections.

With the caveat that follow-up is necessarily short, the results were excellent: All 12 achieved viral suppression within 3 months of treatment initiation, with no virologic rebound to date. They also reported good immunologic responses and high adherence to scheduled injections. These favorable results are all the more remarkable since some of the participants had NNRTI and INSTI resistance mutations, though none had full predicted resistance to either drug.

The experience with these dozen patients is now being reproduced anecdotally in small case numbers from other centers, including our own. While San Francisco led the way, this is doable in any HIV treatment clinic with intensive case management services.

Meanwhile, the DHHS HIV treatment guidelines continue to state the following:

The long-acting ARV combination of injectable cabotegravir (CAB) and RPV is not currently recommended for people with virologic failure [DHHS].

I strongly believe the time has come for us to revise these prohibitory statements (a similar one appears in the IAS-USA guidelines). Such statements may make it difficult for clinicians to procure this treatment for PWH whose treatment options (oral ART) otherwise just aren’t working. One can craft language with appropriate cautionary statements describing the unusual settings in which CAB-RPV is the best — and, importantly, the only — option for people with virologic failure.

Here’s a go at this:

Under rare circumstances, long-acting CAB-RPV can be an option for people with virologic failure when no other treatment options are available or effective. Such treatment must be accompanied by intensive case management and close follow-up. It should be limited to PWH who meet the following criteria:

  • Unable to or cannot take oral ART
  • Are at high risk of HIV disease progression (CD4 < 200 or a prior history of AIDS-defining complications)
  • Have virus susceptible to both CAB and RPV
  • Can be supported by intensive case management services

Sure, there will be cases where treatment failure with resistance occurs; where patients are lost to follow-up; where we will need to battle with payers to convince them to cover this non-FDA–approved indication; where the team of people (and it’s always a team) charged with case-management and medication administration spend enormous time and energy to no avail.

I acknowledge these issues and frustrations, but at the same time, ask — what is the alternative?

It can’t be to withhold the only regimen that might help them. Because as shown in the figure posted below, the median life expectancy for someone with AIDS in the pre-ART era — advanced HIV disease, no treatment — was less than 2 years.

I think we’d all agree that this grim prognosis is simply unacceptable if we have an available effective treatment we’re not using.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.