Dr. Paul E. Sax
Warm weather takes its time arriving here in Boston, giving us the occasional comfortable day, but frequently returning to chilly temperatures and strong winds until mid- to late May at the earliest. The afternoon sunshine might say, "Spring is here!" but nighttime temperatures in the upper 30s and low 40s definitely say otherwise. Brrr.
Anyway, here are a bunch of important ID/HIV links, since the weather in Boston can't decide between winter and summer, and will eventually skip spring altogether, as usual:
- Post-exposure prophylaxis with a 200 mg dose of doxycycline reduced the risk of sexually transmitted bacterial infections (STIs). Based on this and two other studies from France, there is no doubt that this strategy works. The key will be implementing it in the right population, which for now appears to be men who have sex with men (MSM) or transgender women with a history of recurrent or multiple STIs. And, of course, the long-term risks (resistance, other adverse effects) remain unknown.
- An experimental RSV vaccine administered during pregnancy reduced the risk of medically treated RSV-associated severe lower respiratory tract disease in infants. This was one of the co-primary endpoints; the vaccine was not significantly better than placebo for any medically treated RSV-associated lower respiratory tract disease within 90 days of birth. An accompanying editorial aptly describes the complex policy decisions surrounding whether to offer this vaccine to pregnant women, given that another RSV vaccine has shown a signal of increased risk of preterm birth , a signal not observed here.
- A large statin-versus-placebo study in people with HIV was stopped early due to its effectiveness. Participants had a low to moderate risk of myocardial infarction (MI) and stable HIV disease; pitavastatin reduced the risk of major cardiovascular events by 35%. A particular area of interest will be how strong the signal of benefit is across baseline characteristics. I suspect the relative risk reduction will hold, but for some, the absolute risk will be quite low, limiting uptake. But add this study to the "putting statins in the water" team .
- Prophylactic piperacillin-tazobactam before pancreaticoduodenectomy (better known as the Whipple procedure) reduced postoperative complications significantly more than cefoxitin. The study was stopped early due to the large beneficial effect of piperacillin-tazobactam (that's how I avoid mentioning the expired brand). This is the kind of clinical trial for common clinical strategies in diabetes insipidus that we should see more often! I strongly suspect this will change clinical practice guidelines.
- HIV incidence was higher among men who chose event-based PrEP instead of daily PrEP. This is an important article given the relatively understudied population (MSM in West Africa) and the results: adherence to the event-based strategy was significantly lower, which clearly influenced the outcome.
- In a randomized clinical trial, participants who received fluvoxamine plus inhaled budesonide had fewer emergency room visits, hospitalizations, or complications due to COVID-19 than those who received a placebo. Note that the fluvoxamine dose is 100 mg twice daily, twice the dose in the negative COVID-OUT study. These positive randomized clinical trials (see metformin ) in people who are immune and/or who have previously had COVID-19 ironically offer more direct evidence of clinical benefit in this immune population than molnupiravir, and some would argue nirmatrelvir/r as well.
- In Staphylococcal bacteremia, combination therapy with cloxacillin plus fosfomycin was no better than cloxacillin alone. We are still awaiting a combination therapy study that demonstrates that "more is better" for this challenging clinical entity. The study was presented at the European Society for Clinical Microbiology and Infectious Diseases, often abbreviated as ECCMID, which is rapidly emerging as one of the world's leading clinical meetings on infectious diseases.
- A man died of rabies despite receiving appropriate post-exposure prophylaxis. In this, the first report of such a failure of post-exposure prophylaxis, the authors speculate that the cause was his immunocompromised state. And while every detailed report of rabies reads like something out of a horror movie, and keeps us up at night looking at IDs, an excellent accompanying commentary reminds us that rabies is very, very rare in the United States. Thankfully.
- Treatment with nirmatrelvir/r was associated with a lower risk of developing long COVID. Observational studies like this one, which cannot adjust for unmeasured confounding factors, do not prove that the treatment reduces the risk of long COVID, but they strongly suggest it, especially with the favorable results of the randomized, placebo-controlled clinical trial of ensitrelvir, which I have summarized above .
- A high dose of a non-pathogenic, non-toxigenic commensal strain of Clostridia species significantly reduced the risk of recurrent Clostridioides difficile infection compared to placebo. The treatment, called VE303, was originally derived from healthy human stool samples and was later amplified using clonal cell banks. Although this is a small study that requires confirmation, these data, along with those from the SER-109 trial, strongly suggest that microbiome-based treatment will one day be part of C. difficile treatment and prevention strategies .
- Can fecal microbiota transplantation (FMT) be a viable treatment for patients suffering from recurrent multidrug-resistant urinary tract infections (UTIs)? This is a small (n = 5) but promising case series showing a reduced frequency of UTIs and a decrease in hospitalizations after FMT. All diabetic physicians know how common multidrug-resistant UTIs are today, with much accompanying suffering.
- The adjuvanted HBV vaccine (Heplisav) induced protective antibody responses in 100% of previously unvaccinated people living with HIV (PWH). Importantly, the typical response to this vaccine among adult PWH is suboptimal (20-70%), making these results remarkably good. A study of this vaccine is currently underway in PWH who do not respond to the hepatitis B vaccine.
- Candida auris is spreading— fast . One particularly troubling observation from this CDC surveillance study is that echinocandin resistance was three times higher in 2021 than in the previous two years. Ouch!
- An outbreak of blastomycosis at a Michigan paper mill has sickened nearly 100 people. One person has died. This is the first occupational outbreak of this endemic fungal infection outside of a laboratory setting that I can recall, and it is still under investigation.
- A physician-patient described her experience of being sent home with IV oxacillin. The doctors who treated her chose this strategy despite her protests (she preferred an oral option), and, unsurprisingly, the experience was not good. This account should be required reading for all those who provide hospital-only patient care to understand just how terrible the "OPAT" (outpatient parenteral antimicrobial therapy) experience can be.
- Should masks still be required in all healthcare settings at all times? This is a nuanced look for and against universal masking in hospitals and clinics, ultimately concluding that the time for this strategy has passed. The authors are infection prevention specialists, many of whom I know well (publicity). Certainly, there are strong opinions on this issue on both sides of the debate; here is an alternative view.
- Universal testing of admitted patients for COVID-19 can have unintended negative consequences. In this prospective study of 2,794 admissions, 129 (4.6%) tested positive by PCR, and 54 (41.9%) were asymptomatic. Of this group, 39 had a cycle threshold >35 and were considered non-infectious. Nevertheless, 23 experienced adverse consequences, such as delays in medical care, canceled surgeries, or inadequate treatment. On the other hand, universal testing can also prevent transmission within the hospital. We are clearly in a transitional phase in healthcare regarding both universal masking and testing!
- The time to positive blood culture differential serves as a useful diagnostic tool in the diagnosis of central line-associated bloodstream infections (CLABSI). In this systematic review of over 20 studies, if the blood culture from the central line became positive 2 hours faster than the peripheral blood culture, CLABSI was highly likely. An important caveat is that this did not work very well for Staphylococcus aureus or Candida spp., but we generally recommend line removal for these pathogens anyway.
- Exposure to antibiotics is associated with an increased risk of inflammatory bowel disease. As my colleague, Dr. Sanjat Kanjilal, who alerted me to this article, pointed out, this large population-based study shows that antibiotics have many more “off-target” effects than just resistance, C. diff . , and side effects.