Azithromycin for Preschoolers with Wheezing in the Emergency Department

Azithromycin for Preschoolers with Wheezing in the Emergency Department Published May 18, 2026 N Engl J Med 2026;395:753-764 DOI: 10.1056/NEJMoa2516505 Abstract Background Wheezing illnesses are a leading cause of hospitalization for preschool-age children and are frequently treated with antibiotics. Observational studies have shown more frequent isolation of three pathogenic bacteria (Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) from nasopharyngeal samples from children with recurrent episodes of wheezing than from those without such illnesses. Methods In this multicenter trial, we randomly assigned patients 18 to 59 months of age who presented to an emergency department with a moderate-to-severe episode of wheezing to receive azithromycin once daily at a dose of 12 mg per kilogram of body weight or matching placebo for 5 days. The primary outcome was the sum of scores on the Asthma Flare-up Diary for Young Children (ADYC) over 5 days. Primary-outcome scores could range from 5 to 35, with higher scores indicating more severe wheezing-related symptoms. Efficacy was assessed separately in patients who tested positive for pathogenic bacteria (the positive cohort) and in those who tested negative (the negative cohort). Secondary outcomes were length of stay in the emergency department, length of hospital stay, and return emergency department visits or hospitalizations within 72 hours. Bacterial clearance and antimicrobial resistance were measured at follow-up visits 1 to 3 weeks after randomization. Results Among 840 patients who underwent randomization, 521 tested positive for pathogenic bacteria. The trial was stopped for futility by the data and safety monitoring board after a planned interim analysis. ADYC scores did not differ significantly between the azithromycin and placebo groups in either the positive cohort (median, 9.59 [interquartile range, 7.29 to 12.60] vs. 9.72 [interquartile range, 7.66 to 12.17]; P=0.70) or the negative cohort (median, 9.30 [interquartile range, 6.97 to 11.62] vs. 9.10 [interquartile range, 7.19 to 11.45]; P=0.69). In the positive cohort, bacterial clearance was 58.7% in the azithromycin group and 11.4% in the placebo group. Secondary outcomes appeared to be similar in the two groups for both cohorts, as did the development of bacterial resistance and the incidence of adverse events. Conclusions Azithromycin did not lead to 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. (Funded by the National Heart, Lung, and Blood Institute and others; AZ-SWED ClinicalTrials.gov number, NCT04669288.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes The content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, the Health Resources and Services Administration, the Department of Health and Human Services, or the U.S. Government. This article was published on May 18, 2026, at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers UG3/UH3HL147016 for the trial and U24HL147018 for the data coordinating center at the University of Utah, and by the Pediatric Emergency Care Applied Research Network (PECARN). PECARN is supported by the Maternal and Child Health Bureau in the Health Resources and Services Administration of the U.S. Department of Health and Human Services under the Emergency Medical Services for Children (EMSC) program through the following cooperative agreements: EMSC Data Center–University of Utah (UJ5MC30824); Great Lakes–Atlantic Children’s Emergency Research (GLACiER) Node–Nationwide Children’s Hospital (U03MC28844); Hospitals of the Midwest Emergency Research Node (HOMERUN)–Cincinnati Children’s Hospital Medical Center (U03MC22684); Pediatric Emergency Medicine Northeast, West, and South (PEM-NEWS)–Columbia University Medical Center (U03MC00007); Pediatric Research in Injuries and Medical Emergencies (PRIME)–University of California at Davis Medical Center (U03MC00001); Charlotte, Houston, and Milwaukee Prehospital (CHaMP) Research Node–State University of New York at Buffalo (U03MC33154); Seattle, Texas, Los Angeles Research (STELAR) Node–Seattle Children’s Hospital (U03MC33156); and San Francisco–Oakland, Providence, Atlanta Research Collaborative (SPARC) Node–Emory University School of Medicine (U03MC49671). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Elizabeth Beckett Firmage, B.S., from the Arizona Clinical Coordinating Center, University of Arizona, and Krista M. Ellis, M.S., from the Utah Data Coordinating Center, University of Utah, for their assistance with trial management; the research coordinators in PECARN, without whom this trial would not have been possible; the clinicians in PECARN who enrolled children in the trial; the pharmacists who prepared the trial drug and placebo on site; the members of the data and safety monitoring board (Bonnie W. Ramsey, M.D. [chair], Allan Becker, M.D., Michelle Cloutier, M.D., Jeremy Garrett, Ph.D., Haley Hedlin, Ph.D., Carlos Camargo, M.D., Ph.D., and Thomas Terndrup, M.D.); and Francine Ducharme, M.D., for granting permission to use the Pediatric Respiratory Assessment Measure and the Asthma Flare-up Diary for Young Children. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: May 18, 2026 Published in issue: August 20, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. Cited by - No to Azithromycin for Preschoolers with Acute Wheezing in the Emergency Department, New England Journal of Medicine, 395, 8, (818-820), (2026)./doi/full/10.1056/NEJMe2606675 Loading...