To evaluate the impact of adjunctive azithromycin use on postpartum infection rates following cesarean delivery in the United States.
Approach:
Study Design: Retrospective difference-in-differences analysis using Epic Cosmos electronic health record data from 2013 to 2024.
Population: Included nearly 1.7 million deliveries, with 202,234 cesarean deliveries and 1.5 million vaginal deliveries as control.
Outcomes: Primary outcomes were perioperative azithromycin administration and postpartum infection within 6 weeks postdelivery.
Analysis: Adjusted for patient and pregnancy characteristics, comparing outcomes before and after the publication of the C/SOAP trial.
Key Findings:
Perioperative azithromycin use among cesarean deliveries increased from 2% to 40% post-trial publication.
Postpartum infection rates following cesarean delivery decreased from 9% to 8%, while rates for vaginal delivery increased from 2% to 3%.
The adjusted difference-in-differences estimate indicated a 2-percentage-point reduction in postpartum infection, corresponding to a 20% relative decrease.
Several components of the infection composite declined, including endometritis, sepsis, wound infection, and wound disruption.
UTIs increased over time in both delivery groups.
Interpretation:
The real-world reduction in infection was smaller than reported in the C/SOAP trial, with fewer than 50% of cesarean patients receiving azithromycin post-publication.
Limitations:
Scheduled and unscheduled cesarean deliveries could not be reliably distinguished.
The analysis could not account for contemporaneous infection-prevention measures.
Epic Cosmos did not capture all clinical information or care received outside participating systems.
Study population and participating hospitals differed from the broader US population and health care system.
Changes in site participation and reliance on diagnosis codes may have affected results.
Conclusion:
Azithromycin use for pregnant persons undergoing unscheduled cesarean delivery increased and postpartum infection rates decreased in the United States after the trial publication.
