Original Investigation 

Aging and Health

Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks

Joe B. B. Silva, Han-Chih T. Hsieh, Chanelle J. Howe, et al

JAMA Intern Med Published Online: March 30, 2026

doi: 10.1001/jamainternmed.2026.0401

Key Points

Question  Is initiation of antiviral chemoprophylaxis with oseltamivir for 70% or more of eligible nursing home (NH) residents within 2 days of outbreak detection associated with lower 14-day and 30-day mortality and hospitalization compared with a nonintensive approach?

Findings  In this cohort study of 404 influenza outbreaks across 318 NHs with 35 086 resident-trial observations using a sequential target trial emulation and the randomize-censor-weight approach, hospitalization but not death was lower at 14 days post outbreak in NHs that implemented intensive antiviral chemoprophylaxis; 30-day estimates were directionally similar but less precise.

Meaning  Results of this study suggest that clinicians should promptly initiate antiviral chemoprophylaxis in at least 70% of NH residents within 2 days of an influenza outbreak to markedly reduce influenza-related hospitalizations.

Abstract

Importance  Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear.

Objective  To examine 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.

Design, Setting, and Participants  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.

Exposures  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).

Main Outcomes and Measures  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.

Conclusions and Relevance  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.