Azithromycin for Preschoolers with Wheezing in the Emergency Department.

Azithromycin did not show a significant benefit over placebo in reducing wheezing symptoms in preschoolers with moderate-to-severe wheezing.

Summary and findings

This study measured the efficacy of azithromycin in preschoolers aged 18 to 59 months presenting with moderate-to-severe wheezing. Patients received either 12 mg/kg of azithromycin or placebo for 5 days. The trial was stopped for futility, as azithromycin did not significantly reduce wheezing-related symptoms compared to placebo.

Abstract

<h4>Background</h4>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 (<i>Streptococcus pneumoniae</i>, <i>Moraxella catarrhalis</i>, and <i>Haemophilus influenzae</i>) from nasopharyngeal samples from children with recurrent episodes of wheezing than from those without such illnesses.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.).

Limitations

Not reported in abstract.

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