Efficacy of Oseltamivir in Hospitalized Children with Influenza

Background: Oseltamivir is recommended for treatment of all hospitalized children with influenza, with strong recommendations for use in children with high risk conditions, including asthma and complex chronic conditions (CCC), however data on its efficacy is limited. Our objective was to determine whether the use of oseltamivir in the treatment of hospitalized children with influenza is independently associated with improved outcomes.

Methods: We performed a multicenter retrospective cohort study of all children under 18 years of age who were admitted to a participating hospital in the Pediatric Heath Information System (PHIS) database with a diagnosis of influenza from October 2007 to March 2020. We excluded transferred patients and hospitals not reporting data for the entire study period. We compared the outcomes of patients who received oseltamivir on day 0 or 1 of hospitalization with those who did not. We used inverse probability treatment weighting (IPTW) to adjust for severity of disease and address confounding by indication. Our primary outcome was hospital length of stay (LOS). Secondary outcomes included intensive care unit (ICU) LOS, readmission, days treated with positive pressure ventilation (PPV), escalation of care (transfer to ICU after day 1 of admission), use of ECMO, and mortality. We compared continuous outcomes using Wilcoxon rank sum tests and compared dichotomous outcomes using chi squared tests overall and within subgroupings based on age, early ICU admission (defined as ICU charge on day 0 or 1 of hospitalization), history of asthma, and presence of CCC.

Results: 70,473 patients from 36 hospitals were included in the study. Overall 47,071 (66.8%) patients received oseltamivir, with individual hospitals ranging from 43% to 80 %. Table 1 shows demographic and clinical characteristics of included patients. The median LOS was 3 days in both treatment arms, however the IQR was narrower in patients receiving oseltamivir, resulting in a statistically but not clinically meaningful difference. In our weighted analysis we found that patients receiving oseltamivir had lower median ICU LOS (3 vs 4 days), 7 day readmissions (3.8% vs 4.6%), days requiring PPV (5 vs 6 days), mortality (0.9% vs 1.3%) and ECMO use (0.6% vs 0.8%) compared with patients who did not receive oseltamivir (p <0.001 for all), while proportions requiring escalation of care were not different between groups (2.9%, p = 0.7). Figure 1 displays overall results as well as subgroup analyses for specific high risk groups.

Conclusion: Oseltamivir was not uniformly administered to hospitalized children with influenza, but its use was associated with a statistically albeit not clinically significant difference in hospital LOS. Oseltamivir use was associated with a statistically significant reduction in ICU LOS, 7 day readmissions, PPV requirement, mortality, and ECMO use, but had no association with escalation of care.