This Week in Infectious Disease — May 28, 2026

Welcome to This Week in Infectious Disease. This week we're covering 10 notable papers spanning diagnostics and stewardship, new therapies for major global infections, and key updates in public health and epidemiology. Let's dive in.

We begin this week with a focus on diagnostics and antimicrobial stewardship, a constant challenge in an era of rising resistance.

The Study A major open-label randomized trial in JAMA sought to determine the clinical impact of rapid antimicrobial susceptibility testing, or AST, for gram-negative bloodstream infections [6]. The FAST trial randomized over 850 patients in Greece, India, Israel, and Spain to either rapid phenotypic AST performed directly from positive blood cultures or standard AST alone. The primary outcome was a composite measure called the desirability of outcome ranking, or DOOR, at day 30.

Results The investigators found that rapid AST was not superior to standard testing for the primary outcome. The probability that clinical outcomes were more favorable in the rapid testing group was just under 49%, with a confidence interval that crossed the 50% mark, meaning no significant benefit was shown. There was also no difference in 30-day mortality or time to effective antibiotic therapy in the overall population. However, the rapid test did lead to faster changes in antibiotic therapy, with a median time to escalation or de-escalation that was 14 hours shorter than the standard group. This effect was even more pronounced in the prespecified subgroup of patients with carbapenem-resistant infections, where the time to effective therapy was reduced by a median of 18 hours.

Discussion These findings suggest that for an unselected population with gram-negative bacteremia, the availability of rapid susceptibility results may not translate into better overall clinical outcomes, though it does accelerate stewardship decisions. Its utility may be highest in settings with a high prevalence of resistant organisms, where getting to the right drug faster is most critical.

This theme of tailored therapy is central to new recommendations from the 10th European Conference on Infections in Leukaemia, published in The Lancet Infectious Diseases [10]. The panel advocates for a personalized approach to managing febrile neutropenia in patients with hematological malignancies. For hemodynamically stable patients in low-resistance settings, they recommend empirical monotherapy that spares carbapenems. However, for critically ill patients, those with a history of resistant infections, or in high-resistance areas, broader-spectrum therapy is indicated. The guidelines strongly endorse antimicrobial stewardship, including prompt de-escalation once resistant infection is ruled out and discontinuing antibiotics in stable, afebrile patients, regardless of their neutrophil count.

Finally in this section, a study from The Lancet Infectious Diseases highlights diagnostic innovation for mpox in a resource-limited setting [7]. Researchers in Rwanda validated a new mpox-specific IgG ELISA. The assay, which uses four immunodominant antigens, could effectively distinguish individuals with prior infection or vaccination from unexposed individuals. Notably, it showed strong correlation between serum and dried blood spot samples, making it a valuable tool for future population-level surveillance, particularly in outbreak regions where such tools are most needed.

Our next theme is therapeutic advances for some of the world's most significant infectious diseases.

First, a major publication in The New England Journal of Medicine presents Phase 3 results for a new agent against chronic hepatitis B [2]. In two large, replicate trials, patients on stable nucleoside or nucleotide analogue therapy were randomized to receive bepirovirsen, an antisense oligonucleotide, or placebo for 24 weeks. The primary outcome was a functional cure, defined as sustained HBsAg loss and undetectable HBV DNA after stopping all therapy. The results were significant: in both trials, roughly 20% of patients treated with bepirovirsen achieved a functional cure at 72 weeks, compared with zero patients in the placebo groups. While adverse events, particularly grade 3 elevations in ALT, were more common with bepirovirsen, these findings represent a substantial step toward a functional cure for a subset of patients with chronic hepatitis B.

Turning to HIV-associated opportunistic infections, a modeling study in Clinical Infectious Diseases examined the cost-effectiveness of improving care for cryptococcal meningitis in Malawi, a major cause of death among people living with HIV [1]. The analysis showed that improving access to the best available treatment—liposomal amphotericin B, flucytosine, and fluconazole—is highly cost-effective, increasing one-year survival by over 2%. The benefit was even greater when this was combined with an enhanced diagnostic strategy using semi-quantitative serum cryptococcal antigen testing followed by a confirmatory lumbar puncture to detect asymptomatic disease. This combined approach increased one-year survival by 6% and was also deemed cost-effective, highlighting the dual importance of better diagnostics and better treatment access.

Staying with this population, an article in The Lancet Infectious Diseases describes the design of the ATLAS trial, a crucial study addressing a common clinical dilemma in sub-Saharan Africa [9]. The trial was a 2-by-2 factorial study enrolling people living with HIV who were hospitalized with sepsis in Tanzania and Uganda. It aimed to compare immediate, empirical antituberculosis therapy versus waiting for a microbiological or clinical diagnosis. It also compared high-dose rifampicin and isoniazid against standard doses. The primary endpoint was 28-day mortality. It is important to note that the provided abstract describes the trial's methods and population but is incomplete and does not include the final results or conclusions. Nonetheless, it frames a critical question for clinicians managing critically ill patients in high TB-burden settings.

Finally, a commentary in PLoS Medicine reminds us of the power of effective therapy beyond the individual patient [5]. The piece discusses the "Undetectable equals Untransmittable," or U=U, message for HIV prevention. The authors argue that despite the solid biomedical evidence, awareness of U=U remains uneven. Achieving equity requires moving beyond the science alone, with culturally tailored interventions, improved provider education, and supportive policies to ensure this life-changing message reaches all communities and helps dismantle persistent stigma.

Our final section covers new insights in epidemiology and prevention.

A systematic review and meta-analysis in PLoS Medicine provides a stark update on sex differences in tuberculosis prevalence [4]. Analyzing data from 102 prevalence surveys across 33 low- and middle-income countries, the authors found that men consistently experience a higher burden of TB than women. The pooled male-to-female prevalence ratio was 2.02 for bacteriologically confirmed TB, meaning men have roughly double the prevalence. The analysis also suggests this gap may have widened over the past three decades. Interestingly, the disparity was even greater in surveys that screened asymptomatic individuals, suggesting men may harbor a larger, unaddressed burden of subclinical disease.

Next, a review in Nature Reviews Microbiology explores the connection between Varicella Zoster Virus, or VZV, and the central nervous system [8]. The article synthesizes growing epidemiological evidence suggesting that VZV reactivation—shingles—is associated with an increased risk of stroke. There is also growing interest in a potential link with dementia. The authors note that observational studies have reported that zoster vaccination may reduce the risk of these events, but they also highlight complex methodological challenges in interpreting these studies. The review concludes that while the link is compelling, more rigorous investigation is needed before it can be considered definitive and medically actionable, but it points toward a future where zoster vaccination could be a key strategy for healthy aging.

Lastly, we look at pneumococcal vaccination. A long-term follow-up of a cluster-randomized trial in Vietnam, published in The Lancet Infectious Diseases, assessed reduced-dose schedules for the 10-valent pneumococcal conjugate vaccine, or PCV10 [3]. After 5.5 years, a reduced two-dose schedule given at 2 and 12 months of age remained non-inferior to standard three-dose schedules for controlling vaccine-type pneumococcal carriage in infants and toddlers. The study also documented sustained indirect effects, with reduced carriage in unvaccinated caregivers and preschool children. These findings provide strong evidence that dose-sparing schedules can be a sustainable and effective public health strategy, which is critical for vaccine programs worldwide.

If you only have time for one paper this week, make it the Phase 3 results of bepirovirsen for chronic hepatitis B in The New England Journal of Medicine [2]. This is the first time a fixed-duration therapy has demonstrated a significant rate of functional cure in a large-scale trial, representing a major therapeutic milestone for the field.

Here are the key takeaways from this week in Infectious Disease.

First: In diagnostics, the FAST trial showed that rapid susceptibility testing for gram-negative bacteremia did not improve overall clinical outcomes, but it does accelerate appropriate antibiotic changes. Its use should likely be targeted to high-risk patients or settings where multidrug resistance is common.

Second: For Hepatitis B, the antisense oligonucleotide bepirovirsen offers a potential functional cure for approximately one in five patients on existing therapy, a landmark achievement that could change future treatment paradigms.

Third: The tuberculosis burden in low- and middle-income countries is twice as high in men as in women. This persistent and possibly widening gap underscores the need for male-focused engagement and screening strategies in TB control programs.

Fourth: On the vaccine front, reduced-dose PCV10 schedules are effective for long-term control of pneumococcal carriage, supporting dose-sparing strategies. Meanwhile, evidence continues to build for a link between shingles and stroke, highlighting the potential broader benefits of zoster vaccination.

Fifth: For febrile neutropenia, new European guidelines reinforce a personalized, stewardship-centered approach, urging clinicians to spare broad-spectrum agents for the most high-risk patients to preserve their efficacy.

That's your roundup for This Week in Infectious Disease. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.