Treatment of preschool children presenting to the emergency department with wheeze with azithromycin: A placebo-controlled randomized trial

Abstract

Background: Antibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma.

Method: We completed a prospective, double-blinded, randomized placebo-control trial of azithromycin among pre-school children (12 to 60 months of age) presenting to the emergency department with wheeze. Patients were randomized to receive either five days of azithromycin or placebo. Primary outcome was time to resolution of respiratory symptoms after treatment initiation. Secondary outcomes included the number of days children used a Short-Acting Beta-Agonists during the 21 day follow-up and time to disease exacerbation during the following six months (unscheduled health care visit or treatment with an oral corticosteroid for acute respiratory symptoms).

Results: Of the 300 wheezing children recruited, 222 and 169 were analyzed for the primary and secondary outcomes, respectively. The treatment groups had similar demographics and clinical parameters at baseline. Median time to resolution of respiratory symptoms was four days for both treatment arms (interquartile range (IQR) 3,6; p = 0.28). Median number of days of Short-Acting Beta-Agonist use among those who received azithromycin was four and a half days (IQR 2, 7) and five days (IQR 2, 9; p = 0.22) among those who received placebo. Participants who received azithromycin had a 0.91 hazard ratio for time to six-month exacerbation compared to placebo (95% CI 0.61, 1.36, p = 0.65). A pre-determined subgroup analysis showed no differences in outcomes for children with their first or repeat episode of wheezing. There was no significant difference in the proportion of participants experiencing an adverse event.

Conclusion: Azithromycin neither reduced duration of respiratory symptoms nor time to respiratory exacerbation in the following six months after treatment among wheezing preschool children presenting to an emergency department. There was no significant effect among children with either first-time or prior wheezing.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Study participant disposition: Participant screening and enrollment from January 2011 to January 2013 at the Alberta Children’s Hospital, participant randomization and analysis throughout the study and centers.

CONSORT flow diagram of the study enrolment for pre-school wheezing children. a Prescription of Short-Acting Beta Agonist (SABA) at discharge was inclusion criteria for secondary analysis.

Fig 2. Time to symptoms resolution (days) by allocation.

(A), first-time wheezers (B), and previous wheezers (C). There was no significant difference between pre-school children randomized to azithromycin and placebo.

Fig 3. Average change in duration of symptoms (days) in azithromycin versus control treatment arms by subgroup.

Fig 4. Time to respiratory exacerbation by wheeze category.

Kaplan-Meier curve showing time to respiratory disease exacerbation in all randomized participants (A), first-time wheezers (B), and previous wheezers (C). There was no significant difference between pre-school children randomized to azithromycin and placebo.