Adjunctive azithromycin at unscheduled caesarean: 40% uptake, and infection fell

Design

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

Population

1,663,441 singleton live births; 202,234 caesarean and 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)

Caesarean delivery is the commonest operation in the US and the largest single risk factor for postpartum infection. A difference-in-differences analysis of 1,663,441 singleton live births between 2013 and 2024 compared 202,234 caesarean births with 1,461,207 vaginal births, before and after 2016 trial evidence supporting adjunctive azithromycin at unscheduled caesarean.

Azithromycin administration at caesarean rose from 2.2% to 39.6%, while staying at essentially zero for vaginal births - 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, giving an adjusted estimate of -2.0 percentage points (95% CI -2.6 to -1.4). The vaginal comparison is what makes the second figure interpretable: background infection rates were rising, and the caesarean rate moved against that current.

For infection specialists the finding cuts both ways. It is evidence that a clear result changes prescribing without a mandate, and it is evidence that the change takes the better part of a decade and stops at four in ten. If you run antimicrobial stewardship, this is the argument for auditing adoption of beneficial prophylaxis with the same energy applied to restricting unnecessary use - the stewardship literature is heavily weighted towards stopping antibiotics, and getting an indicated one given is the same discipline pointed the other way.

• Audit local administration of adjunctive azithromycin at unscheduled caesarean rather than assuming the protocol is followed.
• Keep the indication precise: unscheduled caesarean, not elective.
• Add under-use of indicated prophylaxis to the stewardship audit cycle, not just over-use.
• Expect adoption of any new prophylaxis to take years - plan the follow-up audit accordingly.
• This is US electronic record data; Indian caesarean rates and infection burden are both high, and local uptake is unmeasured.

Why it matters

Stewardship is usually framed as stopping antibiotics; this shows the equally large gap is the indicated antibiotic that never gets given.

Don't overread it

This is an observational trend analysis - it cannot establish that azithromycin caused the fall in postpartum infection.

The statistics, in plain English

Difference-in-differences subtracts the change in an unexposed group from the change in the exposed group, removing anything that affected both over the same period. The -2.0 percentage point estimate, with a confidence interval of -2.6 to -1.4, is precise because the dataset is enormous. It is still not randomised evidence: other aspects of caesarean care changed across the decade, and this method cannot separate them from the antibiotic.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.