Theodore Lytras1, Elisavet Mouratidou1,2, Anastasia Andreopoulou1, Stefanos Bonovas3,4, Sotirios Tsiodras1,5. 1. Hellenic Centre for Disease Control and Prevention, Athens, Greece. 2. European Programme for Intervention Epidemiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden. 3. Department of Biomedical Sciences, Humanitas University. 4. Humanitas Clinical and Research Center, Milan, Italy. 5. Fourth Department of Internal Medicine, Attikon University Hospital, University of Athens Medical School, Greece.
Abstract
BACKGROUND: The available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically ill patients with influenza of all types. METHODS: The study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICUs) in Greece over 8 seasons (2010-2011 to 2017-2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates. RESULTS: A total of 1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (relative risk, 0.69 [95% credible interval {CrI}, .49-.94]; subdistribution hazard ratio, 0.58 [95% CrI, .37-.88]). This effect was purely due to an increased cause-specific hazard for discharge, whereas the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI, .5-3.5 days). No effect on mortality was observed for A/H1N1 and influenza B patients. CONCLUSIONS: Severely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.
BACKGROUND: The available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically illpatients with influenza of all types. METHODS: The study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICUs) in Greece over 8 seasons (2010-2011 to 2017-2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates. RESULTS: A total of 1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (relative risk, 0.69 [95% credible interval {CrI}, .49-.94]; subdistribution hazard ratio, 0.58 [95% CrI, .37-.88]). This effect was purely due to an increased cause-specific hazard for discharge, whereas the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI, .5-3.5 days). No effect on mortality was observed for A/H1N1 and influenza B patients. CONCLUSIONS: Severely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.
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