Benefit of early treatment with oseltamivir in hospitalized patients with documented 2009 influenza A (H1N1): retrospective cohort study

Background: We assessed the association between early oseltamivir treatment and influenza complications in hospitalized patients. Methods: A retrospective cohort study, including adults with laboratory-confirmed 2009 influenza A (H1N1) in three hospitals in Israel, was performed between July 2009 and January 2010, when admission was limited to high-risk patients. We compared patients treated with oseltamivir early versus late (>48 h after symptom onset). We analysed risk factors for complications, defined as radiographic pneumonia, hypoxia, mechanical ventilation, intensive care unit admission, haemodynamic support or in-hospital death. Risk factors for complications on univariate analysis were entered into a multivariable logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CI) are reported. Results: Four hundred and forty-nine inpatients treated with oseltamivir were included, 189 (42.1%) of whom were treated early. Influenza complications occurred significantly more frequently among patients treated late with oseltamivir [150/260 (57.7%) versus 67/189 (35.4%), P < 0.001]. Late oseltamivir remained significantly associated with complications in the adjusted analysis (OR 2.37, 95% CI 1.52-3.70). Other independent risk factors included dyspnoea, disease severity on admission, lower sodium and treatment at one hospital; rhinorrhoea was protective. In an analysis adjusted for the propensity for early treatment the association remained significant (OR 2.21, 95% CI 1.41-3.46). Initiation of oseltamivir >48 h after admission was associated with a higher rate of complications documented after admission (OR 4.09, 95% CI 1.55-10.80). Severe complications (excluding hypoxia and uncomplicated pneumonia) occurred more frequently with late oseltamivir (adjusted OR 3.28,95% CI 1.56-6.89). Conclusions: Initiation of oseltamivir within 48 h of symptom onset was associated with fewer complications in patients hospitalized with 2009 influenza A (H1N1).