Inappropriate Antibiotic Prescriptions and the Risk of Adverse Drug Events Among Children Treated for Common Infections

Background: Non-guideline antibiotic prescribing for the treatment of pediatric infections is common, but the risk of adverse drug events (ADEs) associated with inappropriate antibiotics is not well-described.

Objectives: To compare the safety of inappropriate vs. appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

Methods: We performed a new-user cohort study with commercially-insured children aged 6 months to 17 years coded with outpatient bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral URI, bronchiolitis, bronchitis, non-suppurative OM) from April 1, 2016 to September 30, 2018. We created a separate cohort for each infection type. For bacterial infections, we categorized oral antibiotic prescriptions dispensed on the infection date as appropriate (first-line agent) or inappropriate (non-first-line agent); for viral infections, we categorized as appropriate (no antibiotic prescription) or inappropriate (antibiotic prescription). We identified individual ADEs using ICD-10-CM diagnosis codes. We selected tendinopathy as a negative control outcome. Outcome-specific follow-up periods ranged from 2—90 days. We used propensity score-weighted Cox proportional hazards models to estimate hazards ratios (HRs) and 95% CIs for the association between inappropriate prescriptions and ADEs. Children were censored at the end of the outcome-specific follow-up period, end of continuous coverage, subsequent antibiotic prescription for a different agent, hospitalization, or end-of-study.

Results: The study included children with bacterial infections (N=1,601,019) and viral infections (N=1,203,226). The proportion of children who received inappropriate antibiotics was influenza (4%), bronchiolitis (9%), viral URI (12%), suppurative OM (31%), pharyngitis (34%), sinusitis (36%), non-suppurative OM (48%), bronchitis (70%). We observed similar risks of tendinopathy among children who received appropriate vs. inappropriate antibiotic prescriptions, regardless of infection type. Among children with bacterial infection, inappropriate antibiotics were associated with increased risk of several ADEs including Clostridioides difficile infection (HR, 4.29; 95% CI, 2.09—8.84 for suppurative OM) and severe allergic reaction (HR, 4.14; 95% CI, 2.48—6.92 for suppurative OM). Inappropriate antibiotics were associated with increased risk of skin rash / urticaria and unspecified allergy for viral URI and non-suppurative OM.

Conclusions: Inappropriate antibiotic prescriptions for common pediatric infections were associated with increased risk of ADEs. These findings support the implementation of outpatient antibiotic stewardship programs.