HIV and ID Observations

An ongoing dialogue on HIV/AIDS, infectious diseases,
all matters medical, and some not so medical.

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November 24th, 2025

ID Things to Be Grateful for — 2025 Edition

Looking back on these annual Thanksgiving posts, I notice an odd pattern: every few years, the intro turns into a kind of apology. As in, Yes, I know the title sounds upbeat, please don’t attack me. The world feels heavy, the ID bad news scrolls by, and there I am writing about gratitude.

A colleague hit the tone perfectly this week when I sent her a minor complaint over email. Her response?

Sorry. Everything sucks. Truly. But it’s my birthday tomorrow, so that’s cool. You can whine anytime.

Yes, that pretty much captures 2025 — equal parts bleak and bemused and sympathetic. And yet, here we are, practicing the small but important task of noticing the good things, and that includes birthdays and ID advances. We do it even amidst the CDC’s decimation, the swelling anti-vaccine chaos, the government shutdown, the canceled global foreign aid, and all the grim funding cuts, with ID research leading the way (in a bad way).

(Plus, Louie’s untimely demise. Still miss you, buddy.)

But hey, we keep going. We always do. So here we go again: A half-dozen solid ID things that happened in 2025 that we can be grateful for as we head into the holiday season.

#1: Lenacapavir Lands

In June, the FDA approved lenacapavir for HIV prevention, instantly giving PrEP a genuinely novel approach. A twice-yearly injection? It still feels a bit like science fiction; no wonder journalists mislabeled it a “vaccine”. Now it is slowly rolling out into practice, and we’ll soon see whether those astonishingly high efficacy numbers from the trials hold up in what is commonly referred to as “the real world”. (Argh, sorry to employ that overused cliche.)

Even better, there’s a deal to supply the drug in low- and middle-income countries for around $40 a year — a staggering improvement in global access. And there’s more in the works: the cleverly named PURPOSE-365 study is testing whether we can go to once-yearly lenacapavir intramuscular injections, and MK-8527 (surely overdue for a real name) is moving forward as a once-monthly oral PrEP pill for those who’d rather avoid needles entirely.

#2: For Bacterial Vaginosis, It’s Time to Treat the Male Partner Too

Bacterial vaginosis (BV) is incredibly common, has several adverse associations, and frequently recurs after treatment — frustrating for both women and the clinicians who treat them. Meanwhile, partner treatment has not been recommended, despite evidence that males harbored some of the same bacterial species implicated in this condition.

Now, along comes the STEP-BV trial, which finally gave us a nicely done study looking at treating male partners. In outpatient clinics in Australia, women with BV and their male partners were randomized to either treatment of the woman only or to treatment of both partners within 1 week of each other.

And here’s the exciting news: Treating the male partner helped a lot, reducing recurrence by 50%, a difference big enough to prompt the data safety monitoring board to stop the study early. It’s not a total solution (recurrence rates were still 35% even in the treatment group), and as with all partner treatments in STIs, implementation will take some thought and involve tricky coordination. But for a condition that’s incredibly common, burdensome, stigmatized, and annoyingly relapsing, this is a big advance.

#3:  SNAP Trial of Staph aureus Bacteremia Yields Its First Major Findings

The long-awaited SNAP trial — the largest randomized study ever done for Staphylococcus aureus bacteremia — finally brought clarity to treatment questions that have lingered since my fellowship days. Conducted across multiple countries (notably excluding the U.S., for reasons that deserve their own rant), SNAP compared cefazolin versus flucloxacillin for methicillin-susceptible Staph aureus (MSSA) and penicillin versus flucloxacillin for penicillin-susceptible strains (PSSA).

The results were refreshingly definitive: cefazolin was noninferior for 90-day mortality and caused less kidney injury, and penicillin was not only noninferior but probably superior for PSSA, with significantly less toxicity. Yes, we really can trust modern penicillin susceptibility testing. (Time to clear that penicillin-allergy label!) After decades of debates about the “inoculum effect” and whether old-fashioned penicillin still has a role, SNAP gives us real evidence to guide care and finally puts some of these perennial controversies to rest.

(Note that both #2 and #3 were led by investigators from Australia, a country with great ID clinical research despite the continent’s low population density. Impressive.)

#4: Dalbavancin Has Its Moment in the Spotlight

For years, dalbavancin sat behind a thick glass case in the hospital pharmacy, next to a sign that might as well have said, “If the patient has no OPAT options and their social situation makes your head hurt — break glass.”

Enter the DOTS trial, which basically told us: Yep, in patients with staph bacteremia, even without challenging discharge factors, this long-acting vancomycin-like drug works just as well as daily intravenous therapy — and it’s so much more convenient! Two doses, separated by a week! Vastly superior to having a PICC line and managing outpatient parenteral antimicrobial therapy (OPAT) for weeks.

Prediction: Based on DOTS, we’ll be seeing a lot more dalbavancin in 2026 and beyond. And honestly? That’s great news for patients and for everyone who has ever tried to arrange home IV antibiotics over a holiday weekend. Now we just need the price to come down and for people to understand that the cost of patient care is not siloed just in the pharmacy budget.

#5:  Cabotegravir-Rilpivirine Expands Its Target Population

The pivotal licensing trials (ATLAS, FLAIR, ATLAS-2M) for cabotegravir-rilpivirine understandably enrolled only our most successfully treated patients — those with no prior treatment failure, no resistance, on first or second regimens. And this population has, historically, done incredibly well with just about any medication switch.

Look, it even got the pole position in my “TYPES OF HIV PAPERS” mash-up.

(Here’s the full version. Dr. Chloe Orkin told me this is my greatest creative accomplishment. Thank you, Chloe, I’ll take it!)

Now, with the CARES, IMPALA, and LATITUDE trials, we know that CAB-RPV works really well even in people with more complex treatment histories. Plus, with the extraordinary effectiveness in those who are viremic and unable to take oral ART — 92% in Atlanta! 98% in San Francisco! — we have a truly transformative approach to ART that can be literally life-saving. A prospective clinical trial of CAB-RPV in people with viremia is enrolling now.

#6: A Novel Malaria Therapy 

Amid all the global-health gloom — funding cuts, program shutdowns, rising resistance — came genuinely great news: a novel malaria treatment with a totally new mechanism of action.

Malaria, remember, still kills hundreds of thousands of people annually, most of them young children. In addition, artemisinin resistance creeps worryingly upwards, threatening our best therapies.

Along comes the drug ganaplacide — it works by disrupting the parasite’s internal protein transport systems and, when combined with the existing drug lumefantrine, looks to be strikingly effective. In a large, phase 3, open-label trial across multiple African countries, the combination of ganaplacide plus lumefantrine (GanLum) demonstrated noninferior activity to standard of care, meeting its primary end point. It was numerically even a bit better, with 97% cured versus 94% in the control arm. There were no concerning safety issues.

The manufacturer estimates it will be approved for use within the next 1–2 years. Hooray!

So yes, some years are better than others for our field of ID, but darkness and gloom notwithstanding, there was still an incredible amount of real progress, brilliant science, and solutions to problems that once felt insurmountable. Hey, half the above examples included long-acting formulations of antimicrobials that would have been unimaginable when I started in ID.*

*Dr. Charles (Charlie) Flexner, King of the Long-Acting Institute of Therapeutics, must be beaming.

As always, I’m grateful for the researchers, clinicians, study participants, nurses, pharmacists, study sponsors, and all the behind-the-scenes people who make these advances possible. And for you, loyal readers, who keep showing up even when the headlines tempt us all to look for new jobs.

Here’s hoping your holiday season includes good health, good company, and at least one conversation where someone asks, “So… what is dalbavancin, anyway?” so you can show off — and, if your Thanksgiving table features that one relative who wants to explain why vaccines are “a government plot,” may your cranberry sauce be extra soothing and your patience infinite.

Happy Thanksgiving, everyone. Let’s hear what you’re grateful for!

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November 18th, 2025

When AI Gets the Medical Advice Wrong — and Right

National Foundation for Infectious Diseases.

A journalist recently reached out to ask about the shingles vaccine. We mostly talked through the usual topics — how common shingles is, why the vaccine works so well, and side effects. Plus, the whole topic of zoster vaccination has been much in the news recently given studies associating receipt of the vaccine with a reduced risk of dementia.

Before we wrapped up, I suggested that hearing from someone who’d had a tough time with shingles might strengthen the piece. A colleague of mine, Lisa Junker (who is Senior Director of Publishing at the Infectious Diseases Society of America), had a serious case involving her ear several years ago.

It was a classic case of herpes zoster oticus, with severe pain, vertigo, and hearing loss. What she memorably said about it when she came back to work: “Shingles:  Do not recommend!” She graciously agreed to speak with the reporter for her WebMD piece.

The article came out, and it’s excellent. I noticed, however, that Lisa had received some wrong counseling from the ENT who cared for her:

Her ENT warned that if shingles returns, it will likely strike the same spot.

This misconception is surprisingly common. It’s right up there with the patient who’s told that waxing and waning symptoms in the same dermatome after an episode represents “recurrent zoster.” It almost never is — which is why this consult is one of the more common outpatient questions we ID doctors receive, and why I wrote about it several years ago. (It’s rarely covered clearly in textbooks or journal articles.)

In short, herpes simplex frequently recurs in the same location, but herpes zoster does not. Recurrent zoster usually (but not always) recurs in a different dermatome altogether, usually several years after the first episode, if it recurs at all — one study found that roughly 10% of people had another episode within 10 years, though this may be an overestimate since there are lots of cases of herpes simplex (and other things) misdiagnosed as herpes zoster.

That’s one of the things about this unpleasant disease. It’s unpredictable. And the ENT’s confident statement that it’s going to come back in the same “spot” — delivered as clinical fact — simply wasn’t correct. I let the reporter know, and she promptly removed the sentence.

And then curiosity got the better of me. Motivated by this New York Times piece that highlighted that patients used AI to get medical advice, I plugged this prompt into two AI tools, OpenEvidence and ChatGPT:

When people get shingles again, is it usually in the same location?

I deliberately left off medical terms such as “dermatome”, “reactivation”, or “recurrent.”

Here’s what happened: OpenEvidence hit the ball out of the park:

Recurrent shingles (herpes zoster) typically does not occur in the same location; it most often affects a different dermatome during subsequent episodes.

With unlimited queries limited to healthcare professionals and medical students, OpenEvidence is currently the best AI tool for medical information. I’ve written about it elsewhere as the “Google for Doctors — and nurses and PAs and anyone with an NPI.” Not only did it provide the correct answer, it offered several highly relevant citations. (Disclosure: NEJM Group, including NEJM Journal Watch, is among the publishers providing content to OpenEvidence.)

ChatGPT? Let’s stick with the same metaphor (can you tell I miss baseball?): it was more Charlie Brown than Aaron Judge, a big whiff:

When someone has more than one episode of shingles, the new episode most commonly appears in the same dermatome as the prior one. This fits the biology: the varicella-zoster virus remains latent in a specific dorsal root (or cranial nerve) ganglion, and reactivates from that same reservoir.

Not just wrong, but wrong with a pathophysiologic justification! Brilliant. This confident but incorrect answer echoed the ENT’s advice and underlies the very misconception that leads to clinical referrals asking about “recurrent” zoster.

When I corrected the model, it “thought” for 35 seconds, then acknowledged the error (“You’re right to push back on that”) and gave the correct answer. It even cited my 2014 blog post! So proud.

But the comparison was a useful reminder of how these systems work: highly fluent, highly confident, occasionally wrong.

And so, in the span of a single afternoon, the same misconception surfaced from three different sources: a clinician, a widely read health article citing that clinician, and an AI model. What can we take from this?

  • Authoritative tone ≠ accuracy. Clinical confidence and AI assurance can all sound convincing, even when the underlying fact is off.
  • AI varies depending on design. Tools that constrain themselves to curated evidence bases (like OpenEvidence) will give more reliable medical answers at baseline; generative models need supervision.
  • Clinician expertise still matters. We’re the interpretive safety net, especially for edge cases, clinical nuance, and information not readily available through standard searches.

In the end, the article was corrected, Lisa is now happily vaccinated, and the real clinical pearl remains the same: If shingles returns, it rarely looks like the first episode.

And it’s definitely worth preventing — both for the first time, and for a recurrence.

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November 13th, 2025

Hot Takes from IDWeek: CDC, COVID, and Two Doses of Dalbavancin

Every so often, you sit down for what’s supposed to be a lighthearted conversation and end up somewhere not just fun, but deeply enjoyable and even profound. That’s what happened when I joined my friends and ID colleagues Drs. Buddy Creech (Vanderbilt, pediatric ID) and Mati Hlatshwayo Davis (Washington University, public health expert) for the Let’s Talk ID podcast. It was recorded live in Atlanta, during the annual IDWeek meeting.

The premise was simple: each of us would share some ID “hot takes.” There was no script, no outline — risky! — but the spontaneity made it especially engaging, mostly because Mati and Buddy are total pros. So what followed was a free-form back-and-forth about the state of infectious diseases and medicine today. And if you listen to the end, you’ll catch an entirely improvised riff on our distinctive names — even mine, short as it is.

My first “hot” take wasn’t especially upbeat but felt important. I said aloud what many of us have been feeling — especially with this year’s IDWeek held in Atlanta, home of the CDC — which is that this proud, indispensable agency is being deliberately weakened, even dismantled, largely as retribution for Covid-era recommendations that became policy.

Hey, we can hold two thoughts in our heads at once! Yes, mistakes were made under grim and confusing circumstances. Who didn’t make mistakes? And yes, the CDC remains an irreplaceable public health institution whose destruction would leave only chaos. Is that really what we want?

During the government shutdown, it was even worse. Painful banners appeared on certain CDC web pages, driving home just how corrosive the mix of politics and public health can be:

Mati, who led St. Louis’s public-health response during the pandemic, put it even more starkly: “You can’t eliminate the infrastructures you say you care about.” She described how fragile those systems already were, and how hard it will be to rebuild them if they collapse. Agree!

Buddy, ever the thoughtful pediatrician, reflected on the paternalism that has crept into our vaccine messaging. He wondered if our vaccine absolutism sowed some of the distrust we’re now reaping. We all agreed that humility, transparency, and a touch of I-don’t-know-yet would have served medicine (and the public) better.

After all that, I tried to lighten things up with something safely clinical: Staphylococcus aureus bacteremia. Two big trials this year — SNAP and DOTS — represented major advances in our field. SNAP showed that cefazolin beats oxacillin/nafcillin for MSSA (and that good old-fashioned penicillin is OK for susceptible strains). DOTS demonstrated that dalbavancin, given just twice, can spare patients weeks of home IV therapy and potentially decompress overburdened OPAT programs.

My next hot take returned to Covid — which, believe it or not, people still get. Ensitrelvir, an oral antiviral similar to Paxlovid, reduced household transmission by about two-thirds in a recent trial (disclosure: I’m a co-investigator). It’s currently under review by the FDA. If approved, we’ll see how this plays out in clinical practice: Will people take a five-day course when someone at home tests positive, or just shrug? Will people test at all? As with influenza post-exposure prophylaxis, those who stand to benefit most are the elderly and immunocompromised — but Covid can still be pretty miserable for everyone.

We closed with a few stories about our names. In my anecdote, I disclosed that when my name is shared over the phone, for some reason people hear the first letter of my last name as an “F” rather than an “S”. But tell me — is there anyone who’s last name is “Fax”? The most reliable way to avoid this error is to say, “My last name is Sax, like the musical instrument.” Of course this sometimes has unintended consequences, as you can see from the highlighted portion of a fax from 2019, shared at the top of this post — which I will treasure forever.

Buddy ended with a moving comment about our community, which I’ll quote because it’s so good:

We want to have solidarity with those groups that we know are struggling right now, whether that’s CDC or local public health officers, folks in academia losing their funding, folks that are struggling to keep up clinical hours, all of the places where all of us are struggling … I have a good friend who has the following quote. He says, “When people get together and they share their successes, it tends to breed competition. When they get together and they share their challenges, it breeds community.” And so I think one of the things that’s special about our community, and it’s on full display here at IDWeek, is that there are times when we celebrate, there are times when we have fun. There are times when we say, how’s it going? And someone’s brave enough to say, it’s not great right now. And that actually deepens our bonds with each other and makes us truly, truly stronger.

Well said, Cruddy Beach!

Categories: Health Care, Infectious Diseases, Medical Education

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November 7th, 2025

Favorite ID Fellow Consults: Johns Hopkins Edition

Lyme disease cases, 2023 (CDC). Each dot represents a new reported case.

Just back from a visit to the Infectious Diseases Division at Johns Hopkins, thanks to the kind invitation of current ID chief Dr. Amita Gupta and her predecessor, Dr. David Thomas.

On a personal note, this visit was only a few decades late. When I applied to medical school, Hopkins never invited me to interview — an awkward omission since my father’s family is from Baltimore, and my aunt had generously offered to host me when I was “interviewing at Hopkins.”

Oops.

That said, all is forgiven. They could not have been more welcoming this time around. In a busy day spent mostly chatting with ID faculty, a highlight was sitting down to lunch with their current ID fellows — and not just because of that delicious lunch.

I asked them a simple question:  What are your favorite ID consults? I already know the greatest hits from our Harvard ID fellows; would responses from another academic powerhouse be similar?

Here’s what they said:

“Patient coughed up a worm.”

A perennial crowd-pleaser, sure to bring gasps of delight when the consult question pops up on the beeper. (We ID doctors are weird.) In hospitalized patients, this is most likely Ascaris lumbricoides — typically when adult worms migrate from the gastrointestinal tract into the respiratory tract, sometimes triggered by anesthesia in patients with a heavy worm burden. Treatment is a single dose of albendazole or mebendazole. And no, they do not require respiratory (or other) precautions.

Fever of unknown origin in a previously healthy person.

Don’t confuse this with fever of “unknown” origin in a patient who has been in the ICU after surgical complications that occurred shortly after Memorial Day, with today being hospital day #160. That’s actually a Fever of Too Many Origins (FOTMO), as brilliantly described by Dr. Harold Horowitz in his classic NEJM piece. (Required reading for all ID docs.) By contrast, true FUO in a previously well patient remains one of the most challenging and intellectually satisfying puzzles in medicine.

Tick-bite infections.

Always gratifying — especially when it’s anaplasmosis and the patient shows that magical overnight response to doxycycline. And in case anyone in New England feels that we have the privilege to be uniquely obsessed with these critters, a glance at the Lyme map shows the mid-Atlantic states are similarly stricken. It’s no wonder long-time Hopkins faculty member Dr. Paul Auwaerter is a lead researcher in the phase 3 Lyme vaccine clinical trial — we eagerly await results!

Exposure history that sounds like a parody of an exposure history.

An example they offered:  A patient from rural Maryland lives on a farm, processes their farm’s poultry on-site in a mobile unit, and works long days in fields and buildings teeming with insects and rodents. Oh, and last week they cleaned out a chicken coop with a leaf blower without wearing respiratory protection. Now, they’re admitted with fever, cough, and pneumonia. You know, your typical ID board certification question, only real life. (For non-medical readers out there, this could be anything — viral, bacterial, fungal, allergic.)

A case right in your ID attending’s wheelhouse.

Imagine the fellow is on service with a world-famous expert in syphilis. A consult comes in for a patient with eye pain, redness, photophobia, and blurred vision; the ophthalmologist has already diagnosed pan-uveitis. The history reveals many high-risk sexual exposures and prior bacterial STIs. You can be sure the attending will be thrilled to deliver a state-of-the-art lecture on syphilitic ocular disease, ready for publication as a review article, references already formatted.

The mystery culture nobody recognizes.

The microbiology lab reports a result that sounds vaguely extraterrestrial, and the primary team panics. Enter ID: “Oh — that’s really just Old Familiar Bug X, renamed Y thanks to the NGS/MALDI-TOF revolution.” Diagnosis: MALDI-TOF-itis*! Treatment: reassurance and something sensible. (*Am I the first person to coin that term? If so, I claim patent rights.)

Fever in a returning traveler.

One of the great ID pleasures: The vicarious thrill of taking a highly detailed travel history. Where did they go? When? What did they eat? Swim in? Where did they sleep? (And with whom, ahem.) Sure, malaria must always be ruled out, but we quietly delight in the diagnostic breadth: dengue, chikungunya, typhoid, rickettsioses, schistosomiasis — and the occasional diagnosis you only see every five years but remember forever.

These are all great examples, and I enjoyed our conversation enormously. And full credit to them for giving me the idea for my latest blog post (this), and for that, I’m grateful enough to send along a free subscription.

And — circling back to my opening question — were their picks similar to those from the Harvard ID fellows? Absolutely. In every program, what excites trainees most is the same rich blend of detective work, unexpected biology, and quirky human detail that draws us to infectious diseases in the first place.

Overall, it was a terrific visit — the kind that reinvigorates your enthusiasm for our field and for the bright future embodied by the next generation, even against today’s storm clouds (about which the less said, the better).

Now, about that medical school interview …

(If you’d like a more informal take on a recent ID headline — the latest listeria outbreak — I’ve written about it on my Substack.)

Categories: Health Care, Infectious Diseases, Medical Education

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October 28th, 2025

Two Covid Vaccine Studies — One Actionable, the Other Not So Much

As we await the results of placebo-controlled Covid-19 vaccine studies, what are we clinicians to do when our patients ask us whether they should get a booster this fall? What once was a no-brainer in the early days of limited immunity to the virus — and the spectacular results of the first placebo-controlled trials — is now a much more nuanced clinical question. Essentially 100% of the population has had either Covid or been vaccinated or both, the disease is on average less severe, the vaccines do have side effects — and who wants another shot anyway?

Now, along comes one of the more clever (cleverer?) observational studies to date addressing this question.

Published here in the New England Journal of Medicine, researchers from the U.S. Department of Veterans Affairs evaluated the 2024–25 Covid-19 vaccine among more than 160,000 veterans who received it on the same day as their flu shot, compared with 130,000 who received the flu shot alone. Participants were followed for six months.

This inclusion of the flu shot only group was absolutely critical, as it diminished the inevitable bias of many observational vaccine studies — which is that those who choose to be vaccinated may intrinsically have more healthy behaviors overall, and that these differences lead to better outcomes, not the vaccines. It’s a form of confounding that no amount of statistical pyrotechnics can completely remove.

Indeed, the “Table 1” of the study, showing baseline characteristics, showed that the group getting the Covid-19 vaccine was quite similar to those who did not, even before statistical adjustment. Hooray. The study included a very typical VA population: age in the early 70s, over 90% were men, and about 18% smoked.

The results?

  • 29% lower risk of Covid-related emergency department visits
  • 39% lower risk of hospitalization
  • 64% lower risk of death

That’s impressive, and I found the mortality results particularly surprising. However, here’s where we need to read the fine print. The relative risk was reduced, but the absolute risk was really small — even in this older patient population. If you’d like a much more detailed review of the paper, I highly recommend Dr. Adam Cifu’s excellent summary, in which he calculates a “number needed to vaccinate” to reduce these endpoints:

Effectiveness is 1-RR, so the relative risks ranged from 0.36 to 0.72 … We can calculate numbers-needed-to-vaccinate (NNV). These come out to 546 for a Covid–associated emergency department visits; 1338 for Covid–associated hospitalization; 4545 for Covid–associated death; and 549 for a composite of these outcomes.

These are pretty big numbers, and would be even higher in a young, healthy cohort. And indeed, if we want a “take-away” message from the study, it’s that we should continue to recommend the Covid vaccine for our older patients, especially those with medical comorbidities.

For a healthy 50-year-old? If they want it and didn’t have side effects from previous vaccinations, I see no contraindications — but it would be inappropriate to use these data to make a broad recommendation that literally everyone should receive an annual Covid vaccine. For that message, the upcoming clinical trials will be informative about other important endpoints, such as the incidence of Covid infection, sick-days averted, and adverse effects.

Separately, you may have seen media coverage of another recent paper — this one in Nature — reporting that mRNA Covid vaccines might somehow “sensitize” tumors to immune checkpoint inhibitors. The idea is intriguing: that vaccination could trigger innate immune pathways, leading to greater tumor responsiveness to immunotherapy. That’s a result that earns splashy headlines and a few hopeful social media posts about mRNA vaccines “helping treat cancer.”

But let’s be clear — this is an early, mechanistic, and hypothesis-generating study, not a clinical trial showing that vaccination improves cancer outcomes. It’s tough-going for non PhD’s to get through the methods and results, which means that most of us clinicians will not be able to critique it appropriately. But at this stage, we can say that the proposed biologic mechanism is speculative, the human data are retrospective, and the observed survival benefit could be confounded by which patients were well enough to receive a vaccine.

So interesting idea, yes! But not a reason to recommend Covid vaccination for cancer therapy or prevention. For now, we should stick to the data that are clinically relevant, as came from the VA study: vaccines continue to reduce serious Covid outcomes in older and high-risk individuals, even if the absolute benefit is smaller than it once was.

Note to readers:  My dog Louie’s death (sniff) prompted me to write some long-form pieces for a newsletter, called PaulSaxMD. (I’m not so good with clever titles, alas.) It will include way less ID esoterica and much more personal stuff. Hope you subscribe!

Cost to you? Same as this NEJM Group blog, what a bargain.

Categories: Health Care, Infectious Diseases, Patient Care

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October 23rd, 2025

What a Difference a Year Makes — with Bonus Halloween Video

At last year’s IDWeek — the annual meeting of the Infectious Diseases Society of America — a group of us veterans in the HIV/ID world wrapped up a busy day of symposia, abstracts, and posters with a lively dinner in Los Angeles.

What do I mean by veterans? If you started your ID training before effective HIV therapy, you qualify: Joe, Trip, Judy, Joel, Jeanne (!!!), me — well, here’s the email I sent after the dinner:

Hi All,

What a fun night! Despite the adventure of getting there in LA crazy traffic (thank you Judy for the lift and your bravery driving in such madness), and the deafening restaurant noise which made us all need to shout, it was a great meal. I awoke today feeling very grateful for having such smart, interesting, and funny long-term colleagues and friends, and optimistic about what’s to come with Jeanne’s exciting new position.

Thanks also to Joel for galvanizing this gathering of us ID docs who did our fellowships in the late 1980s/early 1990s, which was more than 3 decades ago, but who’s counting.

Paul

So what’s the ‘!!!’ doing after Jeanne’s name up there in the second paragraph? That, of course, referred to Dr. Jeanne Marrazzo, who had recently been named Director of the National Institute of Allergy and Infectious Diseases (NIAID), a position she took over from long-time head Tony Fauci. Even though I’ve known Jeanne for years, last year I was a bit star-struck and flattered that she chose to dine with us.

(Maybe she chose us because we all share her love for dogs. Yep, it was that!)

Jeanne spoke about NIAID, the directions she wanted to take it, the challenges our country faced, and just radiated the kind of positive energy that we’d want in this important position. Going from Chief of ID at the University of Alabama to this NIAID head position seemed the right next career step for such a natural born leader. Everything she said exuded optimism, and promise.

Fast forward a year — IDWeek again, this time in Atlanta. You could not imagine a more dispiriting turn of affairs. Right there, in the home city of the CDC, we heard about their laid-off staff and furloughed workers. Barely any CDC officers attended an ID meeting in their hometown — how’s that for irony? Those that did — to showcase their research or to teach us — did so on their own dime, as they’re certainly not receiving a salary or stipend from the organization that they supported for years, sometimes decades.

And what about Jeanne Marrazzo? What’s happened to her?

As has been widely reported, in the year since our dinner she went from celebrated leader to embattled critic. After raising alarms about what she viewed as the politicization of NIAID’s grant process and a growing hostility toward vaccine research, she was placed on administrative leave earlier this year. In September, she and vaccine researcher Dr. Kathleen Neuzil filed a whistleblower complaint alleging retaliation for those concerns. A few weeks later, she was fired — no reason given — but how can we see it as anything other than the silencing of a scientist who spoke up?

(Shared with permission.)

So what a year. From a gleeful dinner in Los Angeles to the sober conference in Atlanta. The same faces, the same field, but the atmosphere flipped upside down by the results of the November election. Last year the energy was forward-looking with a newly minted NIAID director, confident colleagues, and the sense that we were part of something steadily advancing. This year: layoffs, sidelined personnel, “RIFs” — everyone had a story about a grant cancelled, a program blitzed, an international project put on indefinite hold.

And yet — I saw Jeanne at the meeting, and am delighted to say that she’s still bursting with energy and a desire to do something good in the world of Infectious Diseases. Likening herself to a border collie now confined to the house — restless, needing to get out and accomplish some tasks! — she’s looking at numerous options for deploying her various talents. And what a quintessentially on-brand metaphor for herself.

Wherever she ends up will be the better for it, I’m sure of that.

For the rest of us, the times certainly have changed since last October, but the community still felt strong. No, IDWeek 2025 didn’t have the optimistic buzz of last year’s meeting, but nearly everyone I met this year carried the same conviction — that good clinical care, good research, good teaching, and above all, good people, still matter.

Matter a lot.

Now, for that bonus video I promised …

Categories: Health Care, Medical Education, Policy

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October 16th, 2025

Another Bad Week for the CDC, and a Personal Note

On Friday night, news broke that more than a thousand CDC staff received layoff notices — including people who track measles outbreaks, analyze data to craft policy, monitor employee safety, and, remarkably, recent Epidemic Intelligence Service (EIS) fellows (the early-career epidemiologists who often show up first when something alarming appears).

Now, nearly a week later, several of those “reductions in force” (RIFs) are reversed. The whiplash reinforces a dispiriting pattern: act first, think later. Call it the chaos formula:  “flood the zone” and let the fallout be someone else’s problem, the media (both mainstream and social) scrambling to keep up.

A quick word on the euphemism “RIF.” These are not abstractions. These are human beings who chose public service and were told they were fired for no cause. Imagine opening that email after years of outbreak response. The last time I commented on the chaos at CDC, one of the readers articulated a view that I 100% share:

My interactions with the rank and file members of the CDC when I have reached out during Ebola, mpox, and individual patients with rare parasitic infectious diseases showed their wide-open hearts and their knowledge – they cared so much for people they would never meet. My heart aches for this loss, and our patients will be worse for it.

In that post, I further argued that anger over COVID-19 policies fueled these attacks on the CDC. Some of this site’s loyal readers disagreed, saying this would have happened anyway. Their view:  Certain quarters harbor such hostility toward government actions — and especially public health policies — that they now dismantle the CDC just because they can.

In support of my theory, however, a physician I know — one of our former trainees here in Boston — shared a strongly worded critique that began, “With all due respect…” (Never a comforting way to begin.) He viewed the CDC’s pandemic response as a “Chernobyl-level catastrophe,” citing examples such as school closures, toddler masking, the six-foot rule, and universal booster mandates. His plea was for the agency to acknowledge its mistakes and rebuild trust.

Not long after, I received a note from a government official who, while less fiery in tone, made a similar point. He wrote that we in the infectious diseases and public health communities underestimated how angry many Americans felt about being told to follow rules that, to them, never made sense — especially after the first year of the pandemic. He, too, cited the same examples, with a particular emphasis on school closures and rules about childhood masking, both acting as flash points that eroded public confidence and frustrated even medically sophisticated people.

Here’s my view: Two things can be true at once. Some policies were eventually proven to be flawed and dismantling the country’s premier disease-control agency is a terrible form of self-harm. Regarding the former:  In the context of the tremendous unknowns of dealing with a pathogen never before encountered on this planet, could we expect perfection on policies and guidance from any individual or any group?

And were the missteps so grave that we should now systematically gut the institution that in recent history led the responses to Zika, Ebola, and the 2009 H1N1 pandemic? I don’t remember anyone complaining then. If avian influenza accelerates, who coordinates a national response? Do we really want measles to become re-established as a childhood illness in this country without anyone keeping track of outbreaks and trying to intervene? It looks like dengue and Chagas disease are about to take hold here — is anyone watching that? What’s going to happen the next time we need to consult someone with a rare parasitic disease?

We can debate pandemic guidance (please do, for transparency’s sake), past and future. But if we keep cutting the CDC off at the knees, someday there may be nothing left to reform, the damage will be irremediable.

And what then? Rebuild, slowly, during the next public health emergency? Sounds like a recipe for disaster.

Personal note. In other sad news, our dog Louie died this week. We’re heartbroken and grateful for the kind messages so many of you sent. Here’s more information about what happened, plus a remarkable video.

Categories: Health Care, Infectious Diseases, Policy

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October 10th, 2025

DOTS: Optimism Around a “Negative” Dalbavancin Trial

The DOTS randomized clinical trial of dalbavancin versus standard-of-care for Staph aureus bacteremia (SAB) just landed in JAMA, where it undoubtedly will be featured in numerous ID, hospitalist, and medical resident journal clubs over the next several months. Proof:  one of our great second-year ID fellows tagged it immediately for his journal club literally the day it was published.

Led by Drs. Nicholas Turner, Thomas Holland, and a seasoned group of clinical investigators, it didn’t hit superiority on the primary endpoint, but clinical efficacy matched standard therapy.

Here’s why I’m optimistic despite this “negative” study:

  • The primary outcome (Desirability of Outcome Ranking at day 70, DOOR) favored dalbavancin 47.7% of the time. That wasn’t statistically superior to standard care, and explains the cautious tone in the paper. But DOOR mixes clinical response, complications, safety, mortality, and quality of life; failing superiority there is not the same as failing clinically.
  • Clinical efficacy? Essentially equal. On the prespecified noninferiority secondary endpoint, clinical efficacy at day 70 was 73/100 with dalbavancin versus 72/100 with standard therapy (difference 1.0%, 95% CI −11.5 to 13.5). When you focus on the question “Did the patient get better?”, dalbavancin did fine.
  • Think of the comparison — two 1500-mg doses of dalbavancin (days 1 and 8) versus weeks of daily IV therapy. If outcomes are similar and safety is acceptable, this sort of study is exactly how indications and comfort grow for long-acting drugs. No peripherally inserted central catheter (PICC) line! No enrollment in outpatient parenteral antimicrobial therapy (OPAT)! No need for home delivery and storage of medications! No vancomycin levels! Hooray! The accompanying JAMA editorial, by Erin McCreary, PharmD and Dr. Preeti Malani, strikes a similar optimistic tone. Based on many years of hearing patients complain about PICC lines and OPAT, I’m also assuming that the quality of life instrument did not capture the specific tortures of home OPAT we all know and have grown to hate.
  • Who participated really matters. Importantly, patients with left-sided endocarditis, CNS infection, retained infected prosthetic material, or severe immunocompromise were excluded. So although “uncomplicated” SAB was excluded, this wasn’t the everything-and-the-kitchen-sink group either — more like “intermediate complicated,” including right-sided endocarditis and other complicated bacteremias after initial clearance.

The study isn’t perfect, of course, with limitations acknowledged by the authors, but importantly none of them negate the findings. It was open-label, but I’d argue by necessity — the standard-of-care regimens were diverse, and exposing someone to the risks of a PICC line for weeks just for study purposes can’t be justified. Also, the benefits of two infusions would be greatly diluted if everyone had to get daily IVs. With only 200 participants, DOTS was relatively small, with enrollment taking over 2 years despite being open at 23 sites — perhaps because it was hard for investigators to thread the needle on the complicated-but-not-too complicated SAB inclusion criterion. Finally, at least some staph bacteremia is now managed with oral therapy, in particular after clinical stability is achieved with IV; this was not part of the comparison in this study.

(I added that one for you, Dr. Brad Spellberg. You’re welcome.)

OK, elephant in room time:  The infrequent use of dalbavancin for inpatients currently is mostly about money, not microbiology. It’s no secret that if dalbavancin weren’t so eye-wateringly expensive, and if inpatient reimbursement weren’t DRG-based, we’d be using it a whole lot more already.

Price estimates hover in the multi-thousand-dollar range per 500-mg vial or per 1500-mg dose, which is painful for DRG-paid hospital stays even if it saves nursing time and averts line complications later. Who wants to be responsible for a pharmacy budget that includes several thousand dollars for a single antibiotic dose? I reached out to the lead study authors; an economic analysis is in progress.

But let’s back up and take a broader view. We recently heard a talk from Dr. Priya Nori about their experience broadening the use of dalbavancin in their healthcare system, with endorsement from their C-suite. They have found that dalbavancin can be a safe OPAT workaround for patients with barriers to long-term IV access, sometimes enabling earlier discharge and fewer complications, both of which substantially offset the cost (especially the early discharges). The fact that the drug is extremely well tolerated gives additional support for its more widespread use.

So yes, DOTS was “negative” on its primary outcome. But it also showed that dalbavancin performs about as well as what we do now, with far less infrastructure: no PICC, no daily infusions, no vancomycin levels, fewer moving parts. That alone should make the economics work, at least in healthcare systems looking at the global aspects of care rather than just an inpatient antimicrobial pharmacy budget.

Interested in what readers think — will these trial results increase use of dalbavancin for Staph aureus bacteremia? Have at it in the comments.

Categories: Health Care, Infectious Diseases, Patient Care

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October 3rd, 2025

Update on Louie and One Interesting ID Fact

First, I want to express my sincere thanks to all those who commented, emailed, and texted about our dog Louie. My family and I truly appreciate the concern and the feelings people shared about their own dogs.

And how about these selected bits of wisdom, posted by Dr. Gordon Huth?

“Dogs’ lives are too short. Their only fault, really.”—Agnes Turnbull

“The world would be a nicer place if everyone had the ability to love as unconditionally as a dog.”―M.K. Clinton

“Fall in love with a dog, and in many ways you enter a new orbit, a universe that features not just new colors but new rituals, new rules, a new way of experiencing attachment.” ―Caroline Knapp

“The only creatures that are evolved enough to convey pure love are dogs and infants.”―Johnny Depp

“A dog has one aim in life … to bestow his heart.”―J.R. Ackerley

“Dogs have a way of finding the people who need them, and filling an emptiness we didn’t ever know we had.”―Thom Jones

Now, for the update and the background for why I wrote such an alarming post. (For those who tried to read it last week, and the link wouldn’t open, I posted it over here.)

After a very difficult morning walk last week, I took him urgently to the excellent, local animal hospital, Angell Memorial. Well, it was hardly a walk ― he could barely get over the curb, and I had to carry him home. Scary.

The kind veterinarian admitted him overnight, they did an ultrasound and cardiac ECHO, and the next day discharged him home with a terrible diagnosis:  a suspected hemangiosarcoma, leading to a pericardial effusion and ascites, along with likely metastases in the lungs. Here ― take a look at the discharge paperwork (I’ve highlighted some of the low points):

It was quite clear that they did not expect him to live much longer; they also verbally advised us to arrange for home euthanasia within a week. Through sadness and tears, we scheduled it, and I shared the information on this blog because, as I wrote, it was therapeutic.

This has been such a wonderful community all these years, and it didn’t disappoint! Wow, I even heard from non-dog people ― including my mother and my first editor on this site, Mimi Breed. We know you don’t get the dog thing, but we appreciate the sympathy nonetheless.

But guess what? Louie didn’t understand the discharge instructions. Hey, he’s not so great with fancy medical terminology. Plus, he can’t read.

So after the anesthesia from his procedures wore off, he’s pretty much back to his baseline self ― a little less perky, perhaps, but still happy to see us, still eating, still wagging his tail. That’s a new picture of him up there at the top, after he scooted up the stairs. No more of those scary walks, at least not yet.

Look, we’re not in denial ― at least not completely. We’re medical people, after all. The professionals clearly gave him a grim prognosis, and we accept that; he won’t be with us for long. But to quote my wise colleague, social worker extraordinaire Susan Larrabee, you know your dog’s time has come when “your dog can no longer do dog things.” Louie can still do dog things. And that’s good enough for us. Euthanasia on hold, at least for now.

And since this is an ID blog, here’s a closing fact: we literally carry pieces of our dogs with us. Studies show that people and their dogs exchange microbes through shared living space and touch, and that the dog gut microbiome is astonishingly similar to our own ― it’s much closer to humans than to pigs or mice. The study used a microbiome gene catalog containing 1,247,405 genes, which sounds like plenty to me.

So when someone says that a dog becomes part of the family, it’s not just sentiment ― it’s science.

(h/t to Paul E Terrill for sharing this song.)

Categories: Infectious Diseases

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September 26th, 2025

My Dog Louie, the Best Dog Ever, Is Seriously Ill

We got some bad news about our dog Louie, the world’s greatest dog. Writing his story here is therapeutic, so forgive the oversharing.

In January, 2013, my wife forwarded me this email:

She doesn’t usually use 5 exclamation points or 6 question marks, and the unusual punctuation betrayed her excitement. The answer to “What do we do??????”, of course, was to claim one of these puppies; this would be her first dog.

The father of these pups — Asher was his name — was a special dog, a little guy who reigned supreme at the local gift shop, Wild Goose Chase. He greeted visitors with kindness, bright eyes, and a wagging tail, easily claiming his title as The World’s Cutest Dog. His owners even printed up his own card, one my wife kept in her wallet just for this opportunity.

A couple of months later, after Asher’s pups had grown up a bit, we met the very tired mom and the whole gang of her offspring at their home in western Massachusetts. We chose our favorite — a spotted little guy we called Louie, and brought him home to join our family.

Love at first sight.

Louie was no purebred, as the black spots gave away the unfancy part of his genetic lineage. Embark (yes, we checked) told us he was half Coton du Tulear, and half “super mutt,” a term I particularly like. Since this was always cumbersome to explain, when others asked what kind of dog he was, I often just said he was a mix, or a Havanese, since that’s what he looked like and “Havanese” was easier to say.

Over the years, we’ve bonded with Louie in a way that only dog lovers can understand — it’s nothing unusual, but it’s magic nonetheless. Here’s what happened:

  • He immediately learned his name, and responded to it instantly. Of course his name is Louie.
  • He excelled at eye contact, melting your heart. Stare your way to bigger meals.
  • His sleep cycle gradually fell in sync with ours.
  • We learned his loves and hates, based solely on the barking and yipping sounds he’d make at the door when he spotted a favorite (the mailperson who always brought him a Pup-peroni) or an enemy (a black lab that somehow embodied pure evil to him).
  • His tail and bright eyes gave away excitement for every adventure (We’re going to the park!) or incoming snack (Would you like a treat?).
  • Most importantly: He exuded love and adoration for us with zero ambivalence, expressing it regularly without ever, for a moment, getting tired of our company.

The years of love flowing from him made us utterly smitten. Someone came to my office recently, and noted that though the pictures of my family outnumbered the pictures of Louie, the biggest one in size was the painting my son’s friend made of our doggie, in exchange for a contribution we made to an animal services organization. Guilty as charged.

And yes, I’ve featured him here on this site, probably too much, and probably to the annoyance of those who just don’t get the dog thing. A sampling:

  1. There was a post about dog-related infections used as an excuse to post pictures about cute dogs, including Louie.
  2. How about this one about the importance of eye contact in clinical medicine? A perfect chance to show-off Louie’s super skill.
  3. Or another one, about the time he was attacked. He recovered quickly and harbored no hard feelings, what a good dog.
  4. I featured him with my brother’s and sister’s dogs, Zelda and Zoe. Why not?
  5. Here he posed with his favorite dessert plates, the china picked up by my wife in the bargain bin at local store. Yes, we bought a full set.

So lots of Louie here, the Star of the Show on this ID blog.

When I threw his toy or a ball, and he chased after it, he came romping back in a way perfectly embodied by the Charles Barsotti cartoon with the caption, And the crowd roars!

Wow, he learned to wag his tail in exchange for a treat! What a genius! He can even ride a bike!

To the non-animal lovers, I understand this post might not be your cup of tea. This kind of relationship is not for everyone, nor does it have much logic behind it. Why do we grow to love these animals so much? What causes us to generate endorphins when we pet them and stare into their eyes? Why do some people cry more at the death of their dogs than their family members? Makes zero sense.

We thought we had many more years of these tricks, and eye contact, and tail wags ahead.

But for those of us who have experienced it — this deep love for our pets that is returned by them more than a thousand-fold in exchange — I can assure you that watching them get seriously ill is utterly heartbreaking.

Which is why I’m writing this with tears streaming down my cheeks.

Let’s hope you rally, Louie, and that this is just some minor thing from a random scrap you picked up off the street, or a transient viral illness that just gets better with time.

But I am not optimistic. The unspoken messages conveyed by the vet as she told us of the ultrasound findings (we’re doctors, after all), and that she insisted he be admitted to the animal hospital for further workup — these do not engender hope.

I miss you already. ♥

Categories: Health Care

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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