A single oral dose of azithromycin reduced the risk of maternal sepsis or death by 33% in women who delivered vaginally.
The common antibiotic azithromycin has been evaluated for a number of uses, including COVID-19 treatment, sexually transmitted infection (STI) prophylaxis, pneumonia, and pink eye.
Azithromycin also reduces maternal infection in women during unplanned cesarean section delivery. However, it is indeterminable whether azithromycin can reduce maternal and neonate sepsis or death during planned vaginal delivery.
Maternal infection and sepsis, the body’s extreme adverse reaction to infection, are among the top 5 global causes of maternal mortality. Maternal infection can also increase the risk of newborn sepsis, which causes 16% of neonatal deaths.
A recent study, published in the New England Journal of Medicine, sought to determine whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis and/or death if administered prior to planned vaginal birth.
The Azithromycin Prevention in Labor Use Study (A-PLUS; NCT03871491) was a multicountry, placebo-controlled, randomized trial, led by a team of investigators from the University of Alabama at Birmingham. The study was conducted across 8 sites in 7 low- and middle-income countries in Africa, Asia, and Latin America.
From September 2020-August 2022, a total of 29278 women met inclusion criteria and underwent randomization. The women were assigned to either active azithromycin or placebo, with the former group given a single 2-gram dose of azithromycin.
The 2 primary study outcomes were a composite of maternal sepsis or death and a composite of neonatal sepsis or death. During an interim analysis, the data and safety monitoring committee recommended halting the trial for maternal benefit.
The incidence of maternal sepsis or death was found to be 1.6% in the azithromycin group and 2.4% in the placebo group, with a relative risk of 0.67. However, the incidence of stillbirth or neonatal death or sepsis was similar between the active and control groups (10.5% versus 10.3%, respectively), with a relative risk of 1.02.
The investigators noted the difference in the maternal primary outcome was primarily driven by the incidence of sepsis, which was 1.5% in the azithromycin group and 2.3% in the placebo group. Maternal death incidence by any cause was 0.1% in both groups.
The incidence of stillbirth was 0.4% in both the azithromycin and placebo infant cohorts, with neonatal sepsis occurring in 9.8% of the former group and 9.6% of the latter. Neonatal death within 4 weeks after birth occurred in 1.5% of both groups.
Azithromycin was not associated with a higher increase in adverse events. Additionally, secondary outcomes including endometriosis, wound infections, and urine infections, were lower in the azithromycin recipients.
Overall, the study found that a single oral dose of azithromycin reduced the risk of maternal sepsis or death by 33% in women who delivered vaginally. In neonates, however, azithromycin had little effect on sepsis or death.
“In addition to the decrease in maternal infections, there were fewer maternal hospital readmissions and unscheduled visits for care in the first 42 days after delivery, which is consistent with findings from the large United States trial in women who underwent a cesarean birth,” said Waldemar A. Carlo, MD, co-lead of the A-PLUS trial.