Research Summary

Azithromycin Shows No Wheezing-Symptom Benefit in Preschool Children Treated in EDs

Edited by:
Ashton L. Stahl

Key Highlights

  • Azithromycin did not reduce wheezing-related symptom severity versus placebo.
  • The study results were similar whether children tested positive or negative for pathogenic bacteria.
  • Bacterial clearance was higher with azithromycin, but clinical outcomes were not improved.
  • The multicenter trial was stopped early for futility after the interim analysis.

Azithromycin did not result in a greater reduction in wheezing-related symptom severity than placebo among preschool-age children presenting to emergency departments with moderate-to-severe acute wheezing, according to results published in The New England Journal of Medicine. Wheezing illnesses are a leading cause of hospitalization in young children and are frequently treated with antibiotics, but the study found no clinical benefit from azithromycin in this emergency department population.

The multicenter, randomized, placebo-controlled AZ-SWED trial enrolled children aged 18 to 59 months who presented to 8 pediatric emergency departments in the United States with a moderate-to-severe episode of expiratory wheezing. Participants were randomly assigned to receive azithromycin 12 mg/kg once daily or a matching placebo for 5 days. Researchers analyzed outcomes separately among children who tested positive for Streptococcus pneumoniae, Moraxella catarrhalis, or Haemophilus influenzae and those who tested negative for all 3 bacteria.

Study Findings

Among 840 randomized patients, 521 tested positive for at least 1 of the 3 pathogenic bacteria, 312 tested negative, and 7 had an unknown bacterial status. The trial was stopped for futility after a planned interim analysis determined that conditional power was less than 16% in both bacterial-status cohorts.

The primary outcome was the sum of scores over 5 days on the Asthma Flare-up Diary for Young Children, with higher scores indicating more severe symptoms. In the positive cohort, median scores were 9.59 in the azithromycin group and 9.72 in the placebo group (P = .70). In the negative cohort, median scores were 9.30 and 9.10, respectively (P = .69).

Secondary outcomes also appeared similar between treatment groups in both cohorts. Approximately half of all randomized patients were hospitalized. In the positive cohort, 47.9% of patients assigned to azithromycin and 52.5% assigned to placebo were hospitalized; in the negative cohort, the corresponding rates were 48.7% and 50.6%.

Among patients in the positive cohort who returned for at least 1 follow-up visit, bacterial clearance was 58.7% with azithromycin and 11.4% with placebo. However, this difference in bacterial clearance was not accompanied by improvement in wheezing-related symptoms. Development of bacterial resistance and adverse events were similar between groups. No deaths were reported.

Clinical Implications

According to the study authors, the findings suggest that azithromycin should not be used to treat children with established respiratory distress due to moderate-to-severe acute wheezing in the emergency department. The authors noted that early trial stopping limited sample size, precision, and power, although they stated that the results made a moderate or large true effect implausible.

Expert Commentary

“In our trial, azithromycin was not associated with a greater reduction in the severity of wheezing-related symptoms than placebo in preschool-age children who presented to the emergency department with moderate-to-severe acute wheezing,” the researchers concluded.

Reference

Denninghoff KR, Casper TC, Zorc JJ, et al; PECARN AZ-SWED Trial Study Group. Azithromycin for preschoolers with wheezing in the emergency department. N Engl J Med. Published online May 18, 2026. doi:10.1056/NEJMoa2516505