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

Piush J Mandhane,Mary Noseworthy,David W Johnson,William R Craig,Sheldon Spier,Yin Nwe Aung,Patricia Paredes Zambrano De Silbernagel,Janie Williamson,Bonita E Lee,Christophe Leroyer

doi:10.1371/journal.pone.0182411

Piush J Mandhane, Mary Noseworthy + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0182411

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Abstract

BackgroundAntibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma.MethodWe 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).ResultsOf 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.ConclusionAzithromycin 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.

Highlights

Antibiotics are frequently used to treat wheezing children
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
Of the 915 eligible children, 62% (569/915) of families declined to participate in the study, 62 children’s (7%) emergency department attending physician refused inclusion of these children in the study, and 5 (0.5%) children left the emergency department with their parents before enrolment completion (Fig 1)

Summary

Methods

Double-blinded, placebo-control randomized trial of azithromycin among wheezy pre-school children (12 to 60 months of age) who presented to the Alberta Children’s and Stollery Children’s Hospitals’ emergency departments, between January 2011 to May 2014 (S1 File presents the study design). Children were excluded if they used antibiotics in the past 30 days, had a contraindication to the use of a macrolide, significant medical comorbidities, a language barrier, or would not be able to complete follow-up (Table 1 presents the study inclusion and exclusion criteria). The time to symptom resolution between treatment groups was compared using Mann-Whitney U test. We conducted pre-specified subgroup analyses between treatment groups by type of wheeze (first time vs previous). Interaction between treatment effect and a number of baseline characteristics was assessed using Poisson regression.

Results

Discussion

Conclusion