Use of Azithromycin for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants: A Randomized, Double-Blind, Placebo Controlled Trial

Objective Since preventive therapies for bronchopulmonary dysplasia (BPD) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD. Methods Infants less than 1,250 g birth weight were randomized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks. Aspirates were collected during the study to assay for Ureaplasma. The primary endpoints were incidence of BPD or mortality. (Clinical Trials Identifier: NCT00319956.) Results A total of 220 infants were enrolled (n=111 azithromycin, and 109 placebo). Mortality was 18% for the azithromycin group versus 22% for the placebo group (P=0.45). Incidence of BPD was 76% for the azithromycin group versus 84% for the placebo group (P=0.2). The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group, but was not statistically significant. The incidence of BPD in the Ureaplasma subgroup was 73% in the azithromycin group versus 94% in the placebo group (P=0.03). Analysis of patients in the Ureaplasma subgroup only, using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 (0.001-0.618, 95% confidence interval). Conclusions: Routine use of azithromycin therapy for the prevention of BPD cannot be recommended. The early treatment of Ureaplasma colonized/infected patients might be beneficial, but a larger multi-centered trial is required to assess this more definitively. © 2011 Wiley-Liss, Inc