Following a 2016 breakthrough study showing that adjunctive azithromycin halved postoperative infections in unscheduled cesareans, widespread adoption of the antibiotic routine has driven real-world reductions in maternal complications, a new study in JAMA showed.

Before 2016, a little over 2% of cesarean deliveries included prophylactic azithromycin. By 2024, that figure had jumped to nearly 40%, reflecting a major shift in surgical practice.

The results are “a pretty clear demonstration of adoption of an evidence-based change in practice,” said Aaron Caughey, MD, PhD, professor and chair in the Department of Ob/Gyn, and Women’s Health Research and Policy at Oregon Health & Science University School of Medicine in Portland, who was not involved with the study. “Large adoption of a cost-effective addition of a preoperative antibiotic” seems to be associated.

Approximately 1.1 million cesarean deliveries occur in the US annually, accounting for roughly one third of all live births. Among those births, more than 60% are unscheduled. 

But these deliveries increase the risk for postpartum infection up to 20% more than scheduled procedures and five to 10 times more than vaginal delivery.

Researchers sought to assess the real-world use and efficacy of azithromycin in the years following the 2016 publication of a major trial that showed adding the antibiotic to standard cefazolin prophylaxis reduced postoperative infections by 50% in unscheduled cesarean deliveries. Two years following publication, the American College of Obstetricians and Gynecologists (ACOG) said azithromycin should be “considered” for unscheduled cesarean deliveries.

Researchers analyzed observational data from more than 1.6 million live births from 24 to 43 weeks gestation recorded in the national patient dataset Epic Cosmos between 2013 and 2024. Of these, more than 294,000 women with cesarean deliveries received azithromycin.

The increase in use coincided with a measurable decline in postpartum infections within 6 weeks of birth. Postpartum infection rates fell from 9.2% in the 2013-2016 period to 8% in the 2017-2024 period, representing an estimated 20% reduction after adjusting for trends in vaginal deliveries. Trends for the latter remained relatively stable, going from 2% to 2.7% during the same time frames.

Among infection types, sepsis showed the largest decline in cesarean deliveries, dropping from 1.8% to 0.9% between the periods. Surgical site infections decreased from 3.7% to 3.1%, and endometritis declined from 2% to 1.5% over the same periods.

A 20% reduction amounts to the prevention of 6000 infections each year among those delivering via unscheduled cesarean deliveries, said Taylor Freret, MD, a maternal-fetal medicine physician at the Beth Israel Deaconess Medical Center in Boston. Evidence suggests more infections could be prevented if more women receive the treatment.

“It’s really becoming more standard clinical practice, but I would say it’s not quite at the level of it being recommended, and that every single person is getting it,” she said.

In an accompanying editorial, Alan Tita, MD, PhD, University of Alabama at Birmingham, lead researcher of the original azithromycin trial, said that even modest reductions in infection rates could translate into downstream reductions in healthcare costs and hospital readmissions.

“It has implications for where policy stands,” Tita told Medscape Medical News. “Azithromycin has been endorsed by ACOG but not to the extent of saying that they absolutely recommend it — this might move the needle on that recommendation.”

The study authors reported no relevant financial interests.

Steven Ross Johnson is a journalist who covers public health and healthcare delivery issues.