Sie A, Ouattara M, Bountogo M, et al. Azithromycin during Routine Well-Infant Visits to Prevent Death. N Engl J Med. 2024 Jan 18;390(3):221-229. doi: 10.1056/NEJMoa2309495. (Original study)

BACKGROUND: Mass distribution of azithromycin to children 1 to 59 months of age has been shown to reduce childhood all-cause mortality in some sub-Saharan African regions, with the largest reduction seen among infants younger than 12 months of age. Whether the administration of azithromycin at routine health care visits for infants would be effective in preventing death is unclear.

METHODS: We conducted a randomized, placebo-controlled trial of a single dose of azithromycin (20 mg per kilogram of body weight) as compared with placebo, administered during infancy (5 to 12 weeks of age). The primary end point was death before 6 months of age. Infants were recruited at routine vaccination or other well-child visits in clinics and through community outreach in three regions of Burkina Faso. Vital status was assessed at 6 months of age.

RESULTS: Of the 32,877 infants enrolled from September 2019 through October 2022, a total of 16,416 infants were randomly assigned to azithromycin and 16,461 to placebo. Eighty-two infants in the azithromycin group and 75 infants in the placebo group died before 6 months of age (hazard ratio, 1.09; 95% confidence interval [CI], 0.80 to 1.49; P = 0.58); the absolute difference in mortality was 0.04 percentage points (95% CI, -0.10 to 0.21). There was no evidence of an effect of azithromycin on mortality in any of the prespecified subgroups, including subgroups defined according to age, sex, and baseline weight, and no evidence of a difference between the two trial groups in the incidence of adverse events.

CONCLUSIONS: In this trial conducted in Burkina Faso, we found that administration of azithromycin to infants through the existing health care system did not prevent death. (Funded by the Bill and Melinda Gates Foundation; CHAT ClinicalTrials.gov number, NCT03676764.).

Discipline Area Score
Public Health 7 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
Pediatrics (General) 6 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

I did not know about the WHO recommendation of azithromycin mass distribution in regions with high infant mortality rates. Improving the water supply, sanitation, and hygiene are more effective for preventing death in these populations.

Pediatrics (General) rater

The findings that routine azithromycin administration during well-child clinic visits did not reduce mortality in infants is surprising given the fact that previous studies in sub-Saharan regions have demonstrated a reduction in all-cause mortality. This is an important result that needs to be disseminated widely to help reduce prophylactic azithromycin use and minimise anti-microbial resistance.
Comments from EvidenceAlerts subscribers

Prof. jeremy hamilton-miller (2/5/2024 10:04 AM)

What about risks of selecting for azithromycin-resistant organisms?