Background The efficacy and optimal duration of post-exposure influenza prophylaxis with oseltamivir is undetermined in hospital settings where immediate separation from index cases is not feasible. Methods In an open-label non-inferiority randomized clinical trial in a single-center university hospital, the efficacy of 5-day versus 10-day post-exposure prophylaxis with oseltamivir was compared in adult patients exposed to influenza who could not be immediately separated from index influenza cases. Influenza incidence was assessed for 10 days after discontinuing prophylaxis. Results Among 222 exposed patients (median age 75 years; male 119; median Charlson comorbidity index 5), 110 patients were assigned to 5-day group of post-exposure prophylaxis with oseltamivir, and 112 patients to the 10-day group. The median duration of exposure to influenza was 2 days (IQR 1–3 days). In the intention to treat analysis, incidence of influenza was 2/110 (1.8%) in the 5-day group and 0/112 (0%) in the 10-day group (difference, 1.8 percentage points [1-sided 95% CI, –1 to 4.9 p.p.]; P=.77). Conclusions For patients exposed to influenza in a hospital setting, and who were not immediately separated from index cases, post-exposure prophylaxis with oseltamivir resulted in low incidence of nosocomial influenza transmission. Five-day post-exposure prophylaxis was non-inferior to 10-day regimen.
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