Background Understanding of the contributions of respiratory syncytial virus (RSV) and influenza infections to pediatric antibiotic use is limited. We aimed to estimate the proportions and incidence of outpatient antibiotic prescriptions associated with RSV and influenza infections in a sample of commercially-insured US children.

Methods We conducted a retrospective study of outpatient antibiotic prescriptions dispensed to children in the Optum Clinformatics™ DataMart from 2008-2018. We used negative binomial time-series models regressing weekly antibiotic prescriptions against RSV and influenza circulation measures to estimate counterfactual rates of antibiotic prescriptions in the presence and absence of RSV and influenza circulation overall, by age group, census division, and antibiotic class. We considered both syndromic (medical claims) and laboratory (National Respiratory and Enteric Virus Surveillance System) RSV and influenza measures and controlled for age, division, 13-valent pneumococcal conjugate vaccine introduction, and seasonal and secular trends.

Results An estimated 6.3% (95% confidence interval 5.2-7.3%) and 3.4% (3.1-3.8%) of antibiotic prescriptions were associated with RSV and influenza, respectively. These estimates translate to 72.6 (59.7-85.9) RSV-associated and 40.0 (35.1-45.1) influenza-associated antibiotic prescriptions per 1000 children annually. RSV-associated antibiotic prescription incidence was highest among children aged :::5 years while influenza-associated antibiotic prescriptions were highest among children >5 years. Macrolides were the antibiotic class for which RSV and influenza accounted for the greatest share of prescribing.

Conclusions RSV and influenza account for meaningful proportions of pediatric antibiotic prescriptions. Measures to prevent RSV and influenza infections in children, including immunization, may reduce antibiotic use and aid in mitigating antibiotic resistance.

LMK reports consulting fees from Merck Sharpe & Dohme and Vaxcyte for unrelated work. JAL reports research grants from Pfizer for this study and unrelated work and Merck Sharpe & Dohme for unrelated work and consulting fees from Pfizer, Merck, Sharpe & Dohme, Vaxcyte, Seqirus Inc., and Valneva SE for unrelated work. SYT reports research grants from Pfizer for unrelated work. KJB reports research support from Moderna, Dynavax, GlaxoSmithKline, and Pfizer for unrelated work.

This work was supported by the National Institutes of Health [1F31AI174773 to LMK]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by a grant to UC Berkeley from Pfizer (JAL). The funders had no role in the design or conduct of this study, or decision to submit this manuscript.

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Data used in this study is proprietary and available for purchase through the Optum Clinformatics™ DataMart.