- Design
- Multicentre retrospective cohort analysed as a target trial emulation
- Population
- 196 infants aged 12 months or younger hospitalised with pertussis in Italy
- Primary outcome
- Severe course (Pertussis Severity Score >5)
- Effect
- 60% vs 33%; OR 1.80 (95% CI 1.01–3.21), azithromycin vs clarithromycin
This Italian study, published on 3 September, used a target trial emulation framework on records of 196 infants aged 12 months or younger hospitalised with pertussis at 11 centres in 2023–24. Median age was 86 days. Clinicians chose the macrolide; three in four received clarithromycin.
After propensity-score weighting, a severe course (Pertussis Severity Score above 5) occurred in 60% of infants given azithromycin and 33% given clarithromycin (OR 1.80). Azithromycin was also associated with more oxygen use, complications and intensive care admissions. Two infants died, both in the azithromycin group.
Azithromycin is often preferred in young infants because of dosing convenience and the link between erythromycin and pyloric stenosis. Both macrolides are recommended first-line, and this is the first sizeable comparison in hospitalised infants.
It is observational: sicker infants may have been more likely to receive one drug, and weighting cannot fully correct that. The confidence interval only just excludes no difference. It is a reason to watch the question, not to change guidelines on one study.
- Continue to follow national guidance for macrolide choice in infant pertussis; this study does not overturn it.
- Start a macrolide early in any infant with suspected pertussis, without waiting for confirmation.
- Monitor hospitalised infants closely for apnoea, bradycardia and rising white cell count whatever the antibiotic.
- Treat household contacts and check the mother's and siblings' vaccination status.
Why it matters
It questions which macrolide serves the youngest, sickest pertussis patients best.
Don't overread it
This was observational; it cannot show that clarithromycin causes better outcomes.
The statistics, in plain English
An odds ratio of 1.80 with a 95% confidence interval of 1.01 to 3.21 means the lower bound is barely above 1, so the true difference could be very small. With 50 infants on azithromycin, a handful of severe cases either way could shift the result.
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