Clinical Pearls & Morning Reports
Published March 29, 2023
Tita et al. conducted a placebo-controlled trial that evaluated the effect of a single intrapartum oral dose of azithromycin in pregnant persons planning a vaginal delivery on a composite outcome of maternal sepsis or death and a composite neonatal outcome of stillbirth or neonatal death or sepsis. Read the NEJM Original Article here.
Q: Are maternal deaths from infection during the peripartum period on the rise?
A: Maternal infections, particularly sepsis, during the peripartum period account for 10% of maternal deaths and are among the top three causes of maternal death worldwide. The proportion of deaths that are caused by infection has increased over time, whereas deaths from causes such as hemorrhage and preeclampsia have remained stable or decreased.
Q: Did the use of azithromycin reduce maternal peripartum infection during planned vaginal delivery in the trial by Tita et al.?
A: Maternal sepsis or death within 6 weeks after delivery (the composite primary outcome) occurred in 227 of 14,526 patients (1.6%) in the azithromycin group and in 344 of 14,637 (2.4%) in the placebo group (adjusted relative risk, 0.67; 95% confidence interval [CI], 0.56 to 0.79; P<0.001). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). After the interim analysis in which both primary outcomes had been evaluated in approximately 70% of the patients, the data and safety monitoring committee recommended stopping the trial because of maternal benefit.
A: Stillbirth or neonatal death or sepsis within 4 weeks after delivery (the neonatal composite primary outcome) occurred in 1540 of 14,658 infants (10.5%) in the azithromycin group and in 1526 of 14,756 infants (10.3%) in the placebo group (relative risk, 1.02; 95% CI, 0.95 to 1.09; P = 0.56). Neonatal sepsis occurred in 1433 infants (9.8%) and in 1407 infants (9.6%), respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). In each of the two groups, the incidence of stillbirth was 0.4% and the incidence of neonatal death was 1.5%.
A: 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 high prevalence of antibiotic use in non-African sites increases these concerns. Although available studies have not shown significant associations between a single azithromycin dose and sustained carriage of resistant organisms or an increase in resistant infections, more long-term data are needed to inform the association between the routine use of oral azithromycin prophylaxis for vaginal delivery and macrolide resistance patterns and subsequent effects on the microbiome.