Adjunctive azithromycin at unscheduled caesarean: wider use, fewer postpartum infections

Design

Difference-in-differences analysis of electronic health records, 2013 to 2024

Population

1,663,441 US births after labour: 202,234 caesarean, 1,461,207 vaginal

Primary outcome

Perioperative azithromycin use and postpartum infection within 6 weeks

Effect

Azithromycin +37.6 points (33.1 to 42.2); infection −2.0 points (−2.6 to −1.4)

This study used electronic records covering 1,663,441 US births from 2013 to 2024. It compared caesarean births in labour with vaginal births before and after the 2016 trial that showed adding azithromycin to standard prophylaxis reduced infection after unscheduled caesarean. This difference-in-differences design uses the vaginal births as a control for background trends.

Azithromycin use at caesarean rose from 2.2% to 39.6% (adjusted difference-in-differences 37.6 points, 95% CI 33.1 to 42.2). Postpartum infection after caesarean fell from 9.2% to 8.0% while it rose slightly after vaginal birth, giving an adjusted relative fall of 2.0 percentage points (1.4 to 2.6).

The trial evidence is ten years old; what is new is that its effect appears to have carried into routine practice. Six in ten eligible US women still did not receive it. In India, where caesarean rates are high in private hospitals and postpartum infection is common, the gap may be wider. This is observational, so other changes in care over the period may account for part of the fall.

• Consider adding a single dose of azithromycin to standard cephalosporin prophylaxis for caesarean after labour or ruptured membranes.
• Build it into the caesarean order set so it is not forgotten in emergencies.
• Keep the standard pre-incision cephalosporin; azithromycin is added, not substituted.
• Audit uptake locally; four in ten was the US rate eight years after the trial.

Why it matters

A cheap, proven addition is still missed in most eligible caesareans.

Don't overread it

Observational; the fall in infection cannot be attributed to azithromycin alone.

The statistics, in plain English

Difference-in-differences compares the change over time in one group with the change in another group that did not get the intervention, so background trends cancel out. A 2-point fall in absolute terms means about one infection avoided for every 50 caesareans. It is still an observational design, so it supports but does not prove that azithromycin caused the fall.

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