Early Antiviral Prophylaxis Reduces Influenza Hospitalizations in Nursing Homes: Study

Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear. A study was done toexamine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018–May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026. Intensive antiviral chemoprophylaxis with oseltamivir (≥70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Results Among 404 outbreaks in 318 NHs, 35 086 resident-trial observations (29 683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17 155 observations; 17 931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of –0.06% (95% CI, −0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of –0.96% (95% CI, −1.78% to −0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization.

At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death. Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

Reference:

Silva JBB, Hsieh HT, Howe CJ, Gravenstein S, Reich LA, Zullo AR. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Intern Med. Published online March 30, 2026. doi:10.1001/jamainternmed.2026.0401