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Randomized Controlled Trial
. 2025 Oct;60(10):e71314.
doi: 10.1002/ppul.71314.

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

Ricardo A Mosquera  1 , Aravind Yadav  1 , Maria Del Mar Romero-Lopez  2   3 , Ivan G Magana-Ceballos  1 , S Shahrukh Hashmi  4 , Wilfredo De Jesus Rojas  5 , Maria E Tellez  4 , Kaleigh Riggs-Harpur  6 , Fatima M Boricha  4 , Tina S Reddy  4 , Janice L John  4 , Tomika S Harris  4 , Carlos E Rodriguez-Martinez  7 , Jefferson Buendia  7 , Katrina E McBeth  4 , Cindy K Jon  1 , James M Stark  1 , Giuseppe N Colasurdo  1
Affiliations
Randomized Controlled Trial

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

Ricardo A Mosquera et al. Pediatr Pulmonol. 2025 Oct.

Abstract

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.

Keywords: azithromycin; bronchopulmonary dysplasia; chronic lung disease; macrolide.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram for patient enrollment, randomization, and follow up.
See this image and copyright information in PMC

References

    1. Jensen E. A., Dysart K., Gantz M. G., et al., “The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence‐Based Approach,” American Journal of Respiratory and Critical Care Medicine 200, no. 6 (2019): 751–759. - PMC - PubMed
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    1. Mosquera R. A., Gomez‐Rubio A. M., Harris T., et al., “Anti‐Inflammatory Effect of Prophylactic Macrolides on Children With Chronic Lung Disease: A Protocol for a Double‐Blinded Randomised Controlled Trial,” BMJ Open 6, no. 9 (2016): e012060. - PMC - PubMed
    1. Davidson L. and Berkelhamer S., “Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long‐Term Pulmonary Outcomes,” Journal of Clinical Medicine 6, no. 1 (2017): 4. - PMC - PubMed
    1. Mosquera R. A., Avritscher E. B. C., Samuels C. L., et al., “Effect of an Enhanced Medical Home on Serious Illness and Cost of Care Among High‐Risk Children With Chronic Illness,” Journal of the American Medical Association 312, no. 24 (2014): 2640. - PubMed

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