(P24-057-24) Azithromycin for Infants at Risk of Poor Growth and Development: A Pooled Secondary Analysis of Two Randomized Controlled Trials

Objectives: In 2023, the World Health Organization (WHO) revised its guidelines for management of severe acute malnutrition (SAM). The revised guidelines include a new focus, infants at risk of poor growth and development. The guideline identifies evaluation of routine antibiotics for these infants as a priority research area. We pooled data from two large randomized controlled trials evaluating azithromycin for prevention of mortality among infants in Burkina Faso to assess the role of azithromycin in this subgroup of infants.

Methods: Infants in the two trials were 1-12 weeks of age at enrollment. Infants were considered at risk of poor risk of growth and development per WHO: underweight (weight-for-age Z-score, WAZ < -2), wasted (weight-for-length Z-score, WLZ < -2), or MUAC < 11.0 cm among infants ≥6 weeks of age. Infants in both trials were randomized to a single oral (20 mg/kg) dose of azithromycin or matching placebo and were followed until 6 months of age. We evaluated vital status, underweight (WAZ < -2), wasting (WLZ < -2), and stunting (length-for-age Z-score, LAZ) at 6 months among infants at risk of poor growth and development based on WHO single measurement criteria.

Results: A total of 54,709 infants were enrolled in the two trials. Of these, 9,728 were at risk of poor growth and development based on baseline WAZ (N=5,385), WLZ (N=6,022), or MUAC (N=1,541). We found no evidence of a difference in mortality among infants receiving azithromycin vs placebo (1.3% vs 1.1%, risk ratio, RR, 1.18, 95% confidence interval, CI, 0.82 to 1.71). We found no evidence of a difference in any anthropometric endpoint among infants receiving azithromycin vs placebo, including underweight (24.5% vs 25.3%, RR 0.97, 95% CI 0.90 to 1.04), wasting (20.6% vs 20.2%, RR 1.02, 95% CI 0.94 to 1.11), or stunting (17.8% vs 18.8%, RR 0.95, 95% CI 0.87 to 1.04). We found no evidence of a difference in mortality, underweight, wasting, or stunting in any subgroup of infants at risk of poor growth and development defined specifically by low WAZ, low WLZ, or low MUAC (≥6 weeks of age).

Conclusions: In infants aged 1-12 weeks at risk of poor growth and development, we do not have evidence that single dose azithromycin reduces mortality or improves growth outcomes.

Funding Sources: Bill and Melinda Gates Foundation