Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A

Objectives: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. Methods: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. Results: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7 +/- 16.7 versus 18.4 +/- 14.2 days; P = 0.03), hospital length of stay (34.0 +/- 20.3 versus 27.2 +/- 18.2 days; P = 0.001) and MV days (17.4 +/- 15.2 versus 14.0 +/- 12.4; P = 0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR = 1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR = 0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR = 0.44; 95% CI 0.22-0.90; P < 0.001). Conclusions: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.