Azithromycin adoption reduced postpartum infections

After 2016 trial publication, adjunctive azithromycin use rose and postpartum infections fell after unscheduled cesarean delivery.
*Retrospective difference-in-differences cohort study; Level 3.

Citation

Freret TS, Litman E, Wen T, et al. JAMA. Published online September 14, 2026. doi:10.1001/jama.2026.15010

Background

Cesarean delivery is a major risk factor for infection after childbirth. A 2016 trial found that adding azithromycin to standard antibiotics lowered infections during unscheduled cesarean delivery, but real-world uptake was unknown.

Patients

1,663,441 U.S. singleton live births at 24 to 43 weeks in Epic Cosmos, 2013-2024, among people with prenatal care who labored or had prolonged ruptured membranes. Exclusions included intra-amniotic infection, missing delivery mode, inadequate prenatal visits, no documented perioperative antibiotics, and ruptured membranes longer than 5 days.

Intervention

Birth after 2016 trial publication among cesarean deliveries, when adjunctive azithromycin use increased.

Control

Vaginal deliveries over the same periods, used as the comparison group.

Outcome

Perioperative azithromycin use and postpartum infection within 6 weeks.

Follow-up Period

6 weeks after delivery.

Results

Outcome Adjusted effect Clinical meaning
Azithromycin administration +37.6 percentage points (95% CI 33.1 to 42.1) Use increased from 2.2% to 39.6% in cesarean births.
Postpartum infection −2.0 percentage points (95% CI −2.6 to −1.4) NNT 50, if causal; about 20% relative reduction.

Results were adjusted for patient and pregnancy factors. Infection reductions appeared across several infection types; no single component clearly drove the composite.

Limitations

Observational design cannot prove causation. Scheduled versus unscheduled cesarean status was inferred, not directly recorded. Other infection-prevention changes may have contributed. Electronic records may miss infections treated outside participating systems.

Funding

Not reported; some authors disclosed Delfina Care equity.

Clinical Application

Findings reinforce current practice: consider adjunctive azithromycin with standard antibiotics for unscheduled cesarean delivery, while recognizing observational evidence.