Azithromycin and Other Macrolides for Prevention of Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVE: Ureaplasma spp. infection has been associated with bronchopulmonary dysplasia (BPD) in preterm infants. Macrolides have been used for the treatment of Ureaplasma spp. infection, with an intention to prevent BPD. The objective of this meta-analysis is to evaluate the use of macrolides in the prevention of BPD in preterm infants. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, abstracts of the major pediatric society meetings and bibliographies of retrieved articles. We included randomized controlled trials assessing the effects of macrolides therapy on BPD in preterm infants. A random/fixed-effect model was used to synthesize predefined outcomes. RESULTS: Six studies involving 469 preterm infants were eligible for the analysis. Macrolides when used prophylactically (4 studies) did not show significant reduction in BPD (risk ratio, RR, 0.88, 95% confidence interval, CI, 0.75-1.03), death (RR 0.89, 95% CI 0.79-1.01) or in the composite outcome of BPD/death. Similarly, there was no significant reduction in BPD (RR 0.64, 95% CI 0.31-1.31) or the composite outcome of BPD/death (RR 0.41, 95% CI 0.05-3.13), when macrolides were used in Ureaplasma-positive infants. However, prophylactic azithromycin therapy (3 studies) was associated with significant reduction in BPD (RR 0.83, 95% CI 0.71-0.97; number needed to treat, NNT, 10) and composite outcome of BPD/death (RR 0.86, 95% CI 0.77-0.97; NNT 10). CONCLUSION: This meta-analysis demonstrates prophylactic azithromycin therapy was associated with statistically significant reduction in BPD and the composite outcome of BPD/death in preterm infants. However, given the limited information on pharmacokinetics and potential harmful effects, further studies should be done before routine use of azithromycin in the neonatal population.