Azithromycin May Decrease Risk of Mortality, Maternal Sepsis After Vaginal Delivery

A single dose of oral azithromycin was found to be associated with decreased risk for maternal sepsis or mortality among women planning a vaginal delivery. These study results were published in The New England Journal of Medicine.

The Azithromycin Prevention in Labor Use (A-PLUS) study, a double-blinded, placebo-controlled, randomized trial, was conducted between September 2020 and August 2022 in 7 low- to middle-income countries in Africa, Asia, and Latin America. Researchers evaluated whether azithromycin reduced the risk for maternal sepsis or mortality following vaginal delivery. Eligible participants included women (N=29,278) at 28 or more weeks’ gestation who were admitted to the hospital for spontaneous or induced vaginal delivery. Participants were randomly assigned in a 1:1 fashion to receive either a single 2-g dose of oral azithromycin or placebo. The co-primary outcomes were a composite of maternal sepsis or mortality within 6 weeks of delivery and a composite of stillbirth or neonatal death or sepsis within 4 weeks of delivery. Participants were assessed at the first sign of infection and at days 3, 7, 14, 28, and 42 following vaginal delivery. Outcomes between the treatment groups were compared via generalized linear models.

Among participants in the azithromycin (n=14,590) and placebo (N=14,688) groups, the median age was 24 (IQR, 21-28) years, 54.9% and 55.0% resided in Asia, 43.3% and 43.4% were primiparous, and 8.5% and 8.7% were at increased risk for sepsis, respectively.

The researchers found that the rate of maternal sepsis or mortality was lower among participants who received azithromycin vs placebo(1.6% vs 2.4%; adjusted relative risk [aRR], 0.67; 95% CI, 0.56-0.79; P <.001). However, no significant between-group differences were observed for the occurrence of stillbirth or neonatal mortality or sepsis within 4 weeks of delivery (10.5% vs 10.3%).

Subgroup analyses showed similar findings, though azithromycin was associated with a greater maternal benefit among women in Africa (RR, 0.47; 95% CI, 0.36-0.61) vs Asia (RR, 0.88; 95% CI, 0.70-1.10).

Further analysis between participants in the azithromycin vs placebo groups showed low rates of endometriosis (1.3% vs 2.0%) and wound infections (1.6% vs 2.2%), as well as a similar rate of maternal adverse events (7.1% vs 7.6%).

Limitations of this study include insufficient power, variations in the frequency of prophylactic antibiotic use and cesarean birth, and the lack of culture analyses for specific microorganisms.

Despite these findings, “Potential harms of adding routine azithromycin for vaginal deliveries include increased antimicrobial resistance, effects of changes to the maternal or neonatal microbiome, and drug side effects and costs,” the researchers noted.