AZITHROMYCIN did not improve acute preschool wheezing symptoms compared with placebo in an emergency department trial.
Azithromycin for Preschool Wheezing Shows No Symptom Benefit
A multicenter trial found that azithromycin did not reduce wheezing related symptom severity in preschool age children who presented to the emergency department with moderate to severe acute wheezing.
The study enrolled patients 18 to 59 months of age and randomly assigned them to receive azithromycin once daily at 12 mg/kg of body weight or matching placebo for 5 days. Investigators assessed efficacy separately in children who tested positive for pathogenic bacteria and those who tested negative, reflecting prior observational evidence that Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are more frequently isolated from nasopharyngeal samples in children with recurrent wheezing.
The primary outcome was the sum of Asthma Flare-up Diary for Young Children scores over 5 days. Scores could range from 5 to 35, with higher values indicating more severe wheezing related symptoms.
Findings Challenge Antibiotic Use in Acute Wheezing
Among 840 randomized patients, 521 tested positive for pathogenic bacteria. The trial was stopped for futility after a planned interim analysis by the data and safety monitoring board.
Azithromycin for preschool wheezing did not significantly improve diary scores in either bacterial cohort. In the positive cohort, median scores were 9.59 in the azithromycin group and 9.72 in the placebo group. In the negative cohort, median scores were 9.30 and 9.10, respectively.
Secondary outcomes also appeared similar between treatment groups, including emergency department length of stay, hospital length of stay, and return emergency department visits or hospitalizations within 72 hours.
Bacterial Clearance Did Not Translate Clinically
Bacterial clearance was higher among children with pathogenic bacteria who received azithromycin, reaching 58.7% compared with 11.4% in the placebo group. However, this microbiologic effect did not translate into a greater reduction in acute wheezing symptoms.
The development of bacterial resistance and the incidence of adverse events appeared similar between azithromycin and placebo. The findings add to ongoing discussions around preschool asthma, pediatric respiratory infections, and antibiotic stewardship in young children presenting with wheezing in emergency care.
The results suggest that routine azithromycin for preschool wheezing may not offer clinical benefit during moderate to severe emergency department presentations, even when pathogenic bacteria are detected.
Reference
Denninghoff KR et al. Azithromycin for Preschoolers with Wheezing in the Emergency Department. N Engl J Med. 2026;doi: 10.1056/NEJMoa2516505.
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