OBJECTIVES: This study aims to evaluate the impact of macrolide antibiotic use on the risk of recurrent wheezing in infants hospitalized with bronchiolitis, a common but serious respiratory condition in infants.

METHODS: A retrospective cohort study was conducted using nationwide claims data from the Health Insurance Review and Assessment Service. We identified infants aged <1 year hospitalized for bronchiolitis (J21.0-J21.9, ICD-10 code) between 2017.01-2022.04. Participants were divided into 2 groups: patients who received macrolide antibiotics within 2 days of hospitalization (macrolide antibiotic (MA) group) and patients who did not received any antibiotics during the 1^st year of life (control group). Patients who were previously diagnosed with wheeze, high-risk disease, or risk factors of wheezing before index were excluded. For ensuring comparability between groups, 1:1 greedy matching was used for propensity score matching method. The incidence of recurrent wheezing was estimated using Kaplan-Meier curve, and hazard ratio of recurrent wheezing by Cox proportional hazard model. The log-minus-log survival plot and Schoenfeld’s residual were obtained to assess proportional hazard assumption.

RESULTS: The study included 1,107 subjects in each group after matching. In control group, mean age was 3.31 months with 55.19% male. In MA group, mean age was 3.41 months with 54.74% male. The incidence of recurrent wheezing was significantly higher in the MA group (188.07 per 1,000 patient-years) compared to the control group (93.38 per 1,000 patient-years). The risk of recurrent wheezing was 2.06 times higher in the MA group (HR 2.06, 95% CI 1.77-2.36, p<0.0001), with the proportional hazard assumption confirmed as not violated.

CONCLUSIONS: This study suggests a potential association between macrolide antibiotic use and an increased risk of recurrent wheezing in infants hospitalized with bronchiolitis. These findings highlight the need for careful use and reassessment of macrolide antibiotics in the treatment of bronchiolitis.