Evidence to practice, measured: azithromycin at caesarean went from 2% to 40%

Design

difference-in-differences analysis of electronic health record data, 2013-2024

Population

1,663,441 singleton live births; 202,234 caesarean, 1,461,207 vaginal

Primary outcome

perioperative azithromycin administration and postpartum infection within 6 weeks

Effect

azithromycin +37.6 percentage points (95% CI 33.1-42.2); infection -2.0 points (95% CI -2.6 to -1.4)

A difference-in-differences analysis of 1,663,441 deliveries in a large US electronic health record network compared 202,234 caesarean births against 1,461,207 vaginal births, before and after 2016 trial evidence that adjunctive azithromycin reduces postpartum infection at unscheduled caesarean. Use of azithromycin at caesarean rose from 2.2% to 39.6%, while remaining essentially nil at vaginal birth: an adjusted difference-in-differences estimate of 37.6 percentage points (95% CI 33.1 to 42.2).

Postpartum infection within six weeks fell from 9.2% to 8.0% after caesarean, while rising from 2.0% to 2.7% after vaginal birth. The difference-in-differences estimate is -2.0 percentage points (95% CI -2.6 to -1.4). The vaginal birth arm is what makes this more than a before-and-after chart: infection was drifting upwards in the comparison group over the same decade, so the caesarean improvement runs against the background trend rather than with it.

Two things are worth taking from this. One is that a clear trial result reached four in ten eligible operations within eight years, which is both encouraging and slow. The other is the design itself: where a control group exists that was not exposed to the new evidence, the size of a practice change becomes measurable rather than assumed.

• Check whether your unit's caesarean prophylaxis protocol includes adjunctive azithromycin for unscheduled cases.
• Sixty per cent of eligible operations still did not receive it - audit rather than assume local uptake.
• Note the indication is unscheduled caesarean; it does not extend to elective cases on this evidence.
• When judging any 'practice has changed' claim, ask what the unexposed comparison group did over the same period.
• Caesarean rates and postpartum infection burden are both high in Indian practice, but this is US electronic record data and local uptake is unmeasured.

Why it matters

It puts a number on the gap between a trial being published and it reaching the patient, and the number is four in ten after eight years.

Don't overread it

This is an observational analysis of practice trends: it cannot establish that azithromycin caused the fall in infection.

The statistics, in plain English

A difference-in-differences estimate subtracts the change in an unexposed group from the change in the exposed one, which strips out anything affecting both. Here infection after vaginal birth rose 0.7 points while infection after caesarean fell 1.2, giving the -2.0 point net effect. The confidence interval (-2.6 to -1.4) excludes zero comfortably. But this is not a randomised comparison: other caesarean care changed over the same decade, and the method cannot separate those.

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