Azithromycin during routine well-infant visits does not reduce mortality

1. In this randomized controlled trial, infants who received a dose of azithromycin during their routine well visit had comparable mortality rates to placebo.

2. No differences were observed between the azithromycin and placebo groups with regard to rates of caregiver-reported hospitalization, sick-child clinic visits, or adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Previous mass distribution of azithromycin in sub-Saharan regions has been shown to reduce childhood all-cause mortality, particularly among infants one to 11 months of age. Accordingly, the World Health Organization recommends biannual mass distribution of azithromycin to infants in this age range in high-mortality regions. This distribution requires significant coordination and resources, posing several logistical challenges. Providing azithromycin at well-infant visits may be more cost-effective than mass distribution. This trial sought to trial evaluate the effectiveness of azithromycin administration at routine well-infant visits in preventing death in Burkina Faso. Overall, infants who received azithromycin at five to 12 weeks of age did not exhibit lower mortality rates compared to those who received placebo. Further, there was no evidence of a difference between the two groups in the incidence of caregiver-reported hospitalization, sick-child clinic visits, or adverse events. The study was limited by low statistical power as the mortality rates observed in the trial were significantly lower than projected, and community-based recruitment strategies may have unintentionally excluded more vulnerable infants whose parents were unable to attend outreach events. Overall, this study suggests that azithromycin during well-infant visits may not reduce infant mortality.

Click to read the study in NEJM

Relevant Reading: Azithromycin to reduce childhood mortality in sub-Saharan Africa

In-Depth [randomized controlled trial]: This randomized, placebo-controlled trial investigated the efficacy of a single dose of azithromycin administered during routine infancy vaccination visits in preventing infant death in Burkina Faso. Infants were eligible if they were between 5 to 12 weeks of age and were randomly assigned in a 1:1 ratio to receive a dose of azithromycin (20 mg per kilogram) or placebo. The primary outcome was death from any cause before six months of age, and the secondary outcomes included caregiver-reported hospitalization and sick-child clinic visits. Among the 32,877 infants who were initially enrolled in the trial, 16,461 were assigned to azithromycin and 16,461 were assigned to placebo. The age and sex distributions of both groups were similar to those of infants five to 12 weeks of age in the general population. Eighty-two infants in the azithromycin group (0.52%) and 75 infants in the placebo group (0.48%) died before six months of age (hazard ratio, 1.09; 95% Confidence Interval [CI], 0.80 to 1.49; p=0.58), with an absolute difference in mortality of 0.04 percentage points (95% CI, -0.10 to 0.21). No evidence of an effect of azithromycin on mortality was observed in any of the prespecified subgroups. The incidence of caregiver-reported hospitalizations was 1.2% in both groups (relative risk, 0.97; 95% CI, 0.79 to 1.19) and the incidence of sick-child clinic visits was 36.9% and 36.4% in the azithromycin group and placebo group respectively (relative risk, 1.02; 95% CI, 0.98 to 1.06), suggestive of no difference in these secondary outcomes. Moreover, there was no difference in the incidence of adverse events in the two trial groups. In summary, the administration of azithromycin to infants five to 12 weeks of age during routine well-infant visits was not effective in preventing infant death compared to placebo.

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