According to research published today in JAMA, the use of azithromycin during unscheduled cesarean deliveries has risen significantly over the past decade, contributing to a measurable decline in postpartum infections across the United States. Researchers analyzed more than 1.6 million US childbirths to evaluate the adoption of prophylactic azithromycin into clinical practice following a 2016 randomized controlled trial that demonstrated a 50 percent reduction in postpartum infections among women who received the antibiotic prior to cesarean incision compared to those who received a placebo.
Adoption Rates Rise Following Trial and Guideline Endorsements
To determine how clinical practice shifted, a team led by researchers at Beth Israel Deaconess Medical Center in Boston examined electronic health records from hospitals across all 50 states and Washington, DC, using the Epic Cosmos database. The study compared perioperative administration of azithromycin and postpartum infection rates within six weeks of delivery across two distinct timeframes: January 2013 through September 2016, and January 2017 through December 2024. Women undergoing unscheduled cesarean sections formed the intervention group, while those giving birth vaginally served as the control group.
Data show that azithromycin was administered in just 2.2 percent of cesarean births during the pre-trial period from January 1, 2013, to September 28, 2016, compared to 0.01 percent of vaginal births. Following the 2016 trial results, subsequent fetal safety studies, and a 2018 endorsement by the American College of Obstetricians and Gynecologists, use in cesarean deliveries jumped to 39.6 percent between January 1, 2017, and December 2024, while vaginal birth administration crept up only slightly to 0.04 percent. The adjusted difference-in-difference estimate reached 37.6 percentage points.
Real-World Reduction in Postpartum Infections
Postpartum infections occurred in 9.2 percent of cesarean births and 2.0 percent of vaginal births before the trial, according to the findings. In the post-trial period, those rates shifted to 8.0 percent for cesarean births and 2.7 percent for vaginal births, marking an absolute reduction of 2.0 percentage points and a relative reduction of 20 percent. Researchers noted that this translates to roughly 6,000 fewer postpartum infections each year across a variety of conditions, including endometritis, sepsis, and surgical site infections.
Did you know?
Cesarean sections are the most common major surgical procedure in the United States, with nearly one-third of all US births occurring via C-section, and approximately 30 percent of the 1 million cesarean births in 2024 being unscheduled.
The study authors wrote that perioperative azithromycin use at the time of unscheduled cesarean delivery is associated with decreased infection in a large, real-world cohort representative of the US population, supporting the external validity of the 2016 trial. They attributed the smaller relative reduction observed in real-world practice—20 percent compared to 50 percent in the controlled trial—to the fact that less than half of pregnant individuals in the broader study received adjunctive azithromycin.
Public Health Implications and Expert Perspectives
In an accompanying editorial, the lead investigators of the 2016 trial emphasized that population benefits remain substantial. They pointed out that because up to 60 percent, or roughly 720,000, of cesarean deliveries are unscheduled annually in the US, even a modest relative reduction prevents thousands of infections each year and lowers hospital readmissions, antibiotic use, and overall health care costs. According to the editorial authors, failure to implement this strategy represents a missed opportunity to reduce preventable maternal morbidity and potentially mortality.
Frequently Asked Questions
What is adjunctive azithromycin used for during a C-section?
Adjunctive azithromycin is administered prior to a cesarean incision alongside routine pre-incision surgical antibiotics to help prevent postpartum infections such as endometritis and sepsis.
Why did researchers focus on unscheduled cesarean deliveries?
Researchers focused on unscheduled C-sections because postpartum infection rates are nearly two-fold higher in unscheduled C-sections, and electronic health record databases cannot always identify scheduled C-sections with certainty.
How much did azithromycin use increase after the 2016 trial?
According to the JAMA study, administration of azithromycin during cesarean births rose from 2.2 percent before the 2016 trial to 39.6 percent in the subsequent years.
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