Infectious Diseases

Day-4 de-escalation of broad-spectrum therapy in community-onset sepsis appears safe and beneficial

In a target-trial emulation across 67 US hospitals, 36,924 adults with community-onset sepsis receiving empiric broad-spectrum antibiotics were evaluated. Day-4 de-escalation of anti-MRSA or anti-Pseudomonas coverage showed similar 90-day mortality to continued broad-spectrum therapy. De-escalation was associated with fewer antibiotic days by day 14 and shorter hospital length of stay. Secondary outcomes, including in-hospital and 30-day mortality, were otherwise similar, supporting stewardship-driven narrowing once MDR infection is excluded. 1

Ceftriaxone markedly disrupts gut microbiome and resistome in Malawian adults treated for sepsis

This longitudinal metagenomic study in Blantyre, Malawi, tracked stool microbiome and resistome before, during, and after systemic antibiotics for sepsis. Ceftriaxone exposure substantially increased Enterobacterales abundance, suggesting expansion of potentially pathogenic Gram-negative populations in the gut. Ceftriaxone also increased the prevalence of macrolide and aminoglycoside resistance genes within the intestinal resistome. Bayesian modeling and simulations indicated these bystander effects should inform stewardship strategies in low-income settings reliant on ceftriaxone. 2

Nirmatrelvir/ritonavir reduces short- and long-term cardiovascular complications after COVID-19 more than molnupiravir

This Hong Kong target-trial emulation used a territory-wide hospitalized cohort to compare COVID-19 antivirals on cardiovascular outcomes up to one year. Nirmatrelvir/ritonavir use was linked to lower one-year cardiovascular mortality and reduced major adverse cardiac events and multiple cardiac complications. Molnupiravir conferred short-term cardiovascular risk reduction but only marginal long-term cardiovascular mortality benefit. Findings support preferential use of nirmatrelvir/ritonavir over molnupiravir in eligible high-risk hospitalized patients when drug interactions permit. 3

Maternal RSV vaccination and nirsevimab show high real-world protection against infant RSV disease

A US test-negative study enrolled 5,029 children under 2 years with acute respiratory illness at seven pediatric centers during the 2024–2025 RSV season. Among infants younger than 6 months, maternal RSV vaccination was 64% effective against medically attended RSV and 70% effective against RSV hospitalization. Nirsevimab provided 81% effectiveness against RSV hospitalization in infants younger than 8 months at season start or born afterward. Protection from nirsevimab remained high at 130–210 days, supporting its use through an entire RSV season. 4