Adjunctive azithromycin use during unscheduled cesarean deliveries has increased following the landmark C/SOAP trial in 2016, resulting in a decrease in postpartum infection rates in a real-world US cohort.
A difference-in-differences analysis of data from more than 1 million infant deliveries showed that perioperative azithromycin administration during cesarean births increased dramatically from 2.2 percent in January 2013 through September 2016 to 39.6 percent in January 2017 through December 2024. Meanwhile, administration in vaginal births remained low, from 0.01 percent to 0.04 percent. [JAMA 2026;doi:10.1001/jama.2026.15010]
Postpartum infection rates within 6 weeks of delivery decreased from 9.2 percent to 8 percent for cesarean births and increased from 2 percent to 2.6 percent for vaginal births.
“The adjusted difference-in-differences estimate represents a 20-percent relative decrease [in infection rates],” said the investigators led by Dr Taylor Freret from Beth Israel Deaconess Medical Center, Boston, Massachusetts, US.
Freret and colleagues acknowledged that the relative decrease in infection rates is smaller than the 49 percent recorded in the 2016 landmark trial. This difference, they said, may be partly explained by the lower use of perioperative azithromycin for unscheduled cesarean deliveries in clinical practice (<50 percent) vs a 100-percent adherence in the 2016 trial. [N Engl J Med 2016;375:1231-1241]
“We would not expect the mean change during the period from January 2017 to December 2024 to mirror that of the intervention group in the trial, given that practice adoption is increasing over time,” Freret and colleagues said.
Nevertheless, “given that more than 300,000 individuals have an unscheduled cesarean delivery annually, a 20-percent reduction, if due to the use of azithromycin, would still represent a meaningful improvement in postpartum outcomes, potentially preventing 6,000 infections each year,” Freret and colleagues said. [http://wonder.cdc.gov/natality-expanded-current.html]
“These data strengthen the case for more consistent implementation of adjunctive azithromycin in appropriately selected patients and support a move in the American College of Obstetricians and Gynecologists (ACOG) guidelines from ‘consideration’ to ‘recommended use’ in unscheduled, high-risk cesarean deliveries,” wrote Dr Alan Tita from the University of Alabama at Birmingham, Birmingham, Alabama, US, and colleagues in an accompanying editorial. [JAMA 2026;doi:10.1001/jama.2026.16532]
Having an effective prophylaxis, according to Tita and colleagues, is especially important, since the risk of infection is many times higher after cesarean delivery than after vaginal delivery. “Failure to implement [a strategy of administering adjunctive azithromycin] represents a missed opportunity to reduce preventable maternal morbidity and potentially mortality,” they said.
“Future work should refine patient selection and monitor the effects on maternal mortality and global antimicrobial resistance,” Tita and colleagues concluded.
For the present cohort study, Freret and colleagues sourced data from Epic Cosmos. A total of 1,663,441 infant deliveries were included in the analysis. Of these, 202,234 were cesarean births and 1,461,207 were vaginal births. The mean age of pregnant individuals was 29.3 years, and the median BMI at time of delivery was 31.8 kg/m2.