The Effect of Chronic Azithromycin Use in Winter on Health Care Utilization for Children With Bronchopulmonary Dysplasia: A Double Blind Randomized Controlled Study (RCT)

Background Bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, often leads to acute respiratory exacerbations triggered by infections. Our previous mouse study suggested that azithromycin's anti‐inflammatory properties may benefit virus‐induced respiratory illnesses prophylactically. Methods In this single‐center, double‐blind RCT, 60 children (6 months to 6 years) with BPD received azithromycin (5 mg/kg three times weekly; n = 30) or placebo ( n = 30) for one winter season (October to March). Primary outcome was the total number of days of unscheduled healthcare clinic visits, ER visits, and hospital days. Secondary outcomes comprised clinic visits, ER visits, hospital admissions, hospital days, and adverse events. Standard frequentist and Bayesian analyses were used. Results No significant difference in primary outcomes, unscheduled healthcare visits (macrolides 14.9 vs. 4.2 per child‐year; p = 0.1, IRR = 2.1; 95% CI: 0.8−5.4), Bayesian analysis showing 11% probability of benefit; however, high‐risk children (< 2 years, no tracheostomy), rates were lower with the macrolide group (2.7 vs. 4.6 per child‐year; IRR = 0.6; 95% CI: 0.2–1.5), with an 82% probability of benefit. Two outliers in the macrolide group stayed > 40 days in the hospital for non‐medical reasons. For secondary outcomes, we observe a decrease in the intervention group on ER visits (0.5 vs. 1.3 per child‐year; p = 0.047, IRR = 0.4; 95% CI: 0.1−0.9). Hospital days increased (12.1 vs. 1.2 per child‐year; IRR = 9.3; 95% CI: 5.5−16.8). Conclusions Macrolide prophylaxis did not lead to a significant reduction in the primary outcome of unscheduled healthcare encounter days, but subgroup analysis suggests a potential benefit in high‐risk children, with 82% probability of benefit. Trial Registration: NCT02544984.