Large Analysis of Hospitalized Children with Influenza Supports Early Oseltamivir Treatment

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Early oseltamivir use reduced the length of hospitalization and risk for hospital readmission, intensive care unit (ICU) transfers, extracorporeal membrane oxygenation (ECMO) use, and mortality in hospitalized children with influenza, according to new research.

The American Academy of Pediatrics (AAP) and Infectious Diseases Society of America (IDSA) both recommend oseltamivir for the treatment of all hospitalized children with influenza. These recommendations are based on findings that outpatient oseltamivir administration improves the median time to alleviation of symptoms over placebo among children by approximately 29 hours.

“Despite these guidelines, there is debate as to whether oseltamivir improves patient outcomes or reduces resource use in hospitalized patients,” wrote researchers led by Patrick Walsh, MD, MS, of Cincinnati Children’s Hospital Medical Center, in Ohio, in the study published in JAMA Pediatrics. “Given these limitations and the lack of randomized clinical trial (RCT) data available, hospitalized children remain the population with the largest gap in evidence for oseltamivir treatment.”

Walsh and colleagues conducted a multicenter retrospective study of 55 799 children aged less than 18 years who were hospitalized with influenza from October 1, 2007, to March 31, 2020, in 36 tertiary care pediatric hospitals. They aimed to assess the effects of early oseltamivir treatment, defined for the purpose of the study as use of oseltamivir on hospital days 0 or 1.

The primary outcome was hospital length of stay (LOS) in calendar days and secondary outcomes included 7-day hospital readmission, late ICU transfer (ie, transferred on or after hospital day 2), and a composite outcome of in-hospital death or use of ECMO, according to the study.

Researchers compared outcomes among participants who did and did not receive early oseltamivir treatment using multivariable generalized linear mixed-effects models, with adjustments made for demographic characteristics, comorbidities, and illness severity. Inverse probability treatment weighting (IPTW) based on propensity scoring was used to address confounding by indication.

Among the total study population, the median age was 3.61 years, 56% were boys, and 59.5% received early treatment with oseltamivir. Of the 22 592 children who did not receive early oseltamivir treatment, 7% were treated with oseltamivir on hospital day 2 or later and 33% were never treated with oseltamivir.

In the IPTW analysis, investigators found that children treated with early oseltamivir had reduced LOS (median, 3 vs 4 days; IPTW model ratio, 0.52; 95% CI, 0.52-0.53), all-cause 7-day hospital readmissions (3.5% vs 4.8%; adjusted odds ratio [aOR], 0.72; 95% CI, 0.66-0.77), late ICU transfer (2.4% vs 5.5%; aOR, 0.41; 95% CI, 0.37-0.46), and the composite outcome of death or ECMO use (0.9% vs 1.4%; aOR, 0.63; 95% CI, 0.54-0.73) compared to participants who did receive early oseltamivir treatment. The mixed-effects models showed similar results, according to the team.

“Our data support the current recommendations by the AAP and IDSA for oseltamivir use early in influenza disease course for hospitalized children,” concluded Walsh et al.

Limitations include the inability to determine whether all participants had laboratory-confirmed influenza and the lack of clinical information, including illness history, physical examination findings, and laboratory test results. Moreover, some participants that were classified as having never received oseltamivir may have received oseltamivir as outpatients prior to enrollment.

Reference: Walsh PS, Schnadower D, Zhang Y, et al. Association of early oseltamivir with improved outcomes in hospitalized children with influenza, 2007-2020. JAMA Pediatr. 2022;176(11):e223261. doi:10.1001/jamapediatrics.2022.3261