Top 5 Infectious Disease News Stories Week of August 30 to September 6

FDA Accepts Shionogi’s NDA for Ensitrelvir Oral Antiviral in COVID-19 Postexposure Prevention

The US Food and Drug Administration (FDA) has accepted Shionogi’s new drug application for ensitrelvir, an investigational oral antiviral for the prevention of COVID-19 following exposure, with a Prescription Drug User Fee Act decision expected by June 16, 2026. The application is supported by phase 3 SCORPIO-PEP trial results, which demonstrated a 67% relative risk reduction in symptomatic COVID-19 compared with placebo (2.9% vs 9%; risk ratio, .33; 95% CI, .22-0.49; P < .0001), with consistent findings across broader analyses. Ensitrelvir, a SARS-CoV-2 main protease inhibitor marketed as Xocova in Japan and Singapore, was well tolerated with adverse events comparable to placebo and is also under regulatory review in Europe, Taiwan, and other regions. If approved, it would be the first oral antiviral available in the United States for postexposure prophylaxis of COVID-19.

Monitoring Drug-Resistant Strains of Malaria Utilizing Genomic Sequencing

The University of North Carolina’s Institute for Global Health and Infectious Diseases (IGHID) is scaling genomic surveillance of drug-resistant malaria in the Democratic Republic of the Congo (DRC), supported by a $2.9 million grant for the countrywide PaluSeq program to monitor antimalarial resistance mutations. The initiative, led by Jonathan Parr, MD, MPH, combines field epidemiology with high-throughput laboratory sequencing to generate “report cards” showing where and how frequently resistance markers occur, informing national treatment and control decisions amid rising pockets of resistance and no widely available alternative therapies. The effort targets a high-burden setting, sub-Saharan Africa accounted for 94% of malaria cases and 95% of deaths in 2023, with the DRC contributing an estimated >30 million cases and >80,000 deaths (mostly in young children), and carries relevance for US public health given recent, limited locally acquired cases and climate- and vector-related risks. IGHID’s approach aims to guide responsive drug policy while building local capacity for sustained molecular surveillance.

RSV Vaccine Trial Findings Show Reduced Cardiorespiratory Hospitalizations in Older Adults

A prespecified analysis of the DAN-RSV randomized trial found that a bivalent RSV prefusion F protein–based vaccine (RSVpreF) significantly reduced all-cause cardiorespiratory hospitalizations in adults aged 60 years or older but did not yield statistically significant reductions in cardiovascular-specific events. Among 131,276 participants in Denmark during the 2024–2025 winter season, incidence of all-cause cardiorespiratory hospitalization was 26.3 versus 29.2 per 1000 participant-years for vaccinated and control groups, respectively (vaccine effectiveness, 9.9%; 95% CI, .3%-18.7%; P = .04). Outcomes for myocardial infarction, heart failure, atrial fibrillation, and stroke were directionally lower but nonsignificant, including stroke (3 vs 3.8 per 1000 participant-years; vaccine effectiveness, 19.4%; 95% CI, –8.6% to 40.4%; P = .14). Investigators noted potential downstream cardioprotective effects but emphasized study limitations, including the open-label design, reliance on registry and routine testing, limited statistical power for cardiovascular endpoints, and homogeneity of the study population. Findings support RSV immunization’s role in reducing overall cardiorespiratory burden among older adults while leaving cardiovascular-specific benefits uncertain.

High-Dose Influenza Vaccine vs Standard Dose: Hospitalization Outcomes in Older Adults

A pragmatic randomized trial in Denmark involving 332,438 adults aged 65 years or older found no statistically significant difference between high-dose and standard-dose inactivated influenza vaccines in preventing hospitalizations for influenza or pneumonia over three influenza seasons (2022–2025). Hospitalization occurred in .68% of high-dose recipients versus .73% of standard-dose recipients (relative vaccine effectiveness, 5.9%; 95% CI, –2.1% to 13.4; P = .14). High-dose vaccination was associated with fewer influenza-coded hospitalizations (.06% vs .11%; relative effectiveness, 43.6%; 95% CI, 27.5%–56.3%) but not with pneumonia, cardiorespiratory outcomes, or all-cause hospitalizations. Serious adverse events occurred at similar rates in both groups, supporting comparable safety. Limitations included the open-label design, reliance on administrative data, limited virologic confirmation, and potential misclassification during the COVID-19 era. Findings suggest that while high-dose vaccination may reduce influenza-coded hospitalizations, overall benefit beyond standard-dose vaccination for older adults remains uncertain.

The Aminoglyco-Side Hustle: What’s Now and Next in Gram-Negative Infections

Aminoglycosides, once a mainstay of gram-negative infection management, have seen declining use as newer agents with targeted activity and improved safety profiles have emerged. Recent Clinical and Laboratory Standards Institute breakpoint revisions lowered susceptibility thresholds for Enterobacterales and Pseudomonas aeruginosa, limiting aminoglycoside utility to combination therapy for systemic infections. Their strongest role now lies in urinary tract infections, where single-dose regimens achieve high urinary concentrations, favorable cure rates, and activity against multidrug-resistant pathogens. The Infectious Diseases Society of America currently recommends aminoglycosides as alternatives for uncomplicated cystitis and complicated UTI, including those due to extended-spectrum β-lactamase or carbapenem-resistant organisms. Research into toxicity mitigation, such as coadministration with the leukotriene inhibitor zileuton, and renewed interest in veterinary-derived agents like apramycin, suggest potential future applications. While concerns over nephrotoxicity and mixed efficacy limit broader use, evolving strategies may preserve aminoglycosides as part of the therapeutic arsenal against multidrug-resistant gram-negative infections.