A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial

Gabrielle B Mccallum,Andrew V White,Peter S Morris,Ian M Mackay,Carolyn Maclennan,Mark D Chatfield,Anne B Chang,Theo P Sloots,Hideyuki Sawada

doi:10.1371/journal.pone.0074316

Abstract

ObjectiveBronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology.MethodsChildren aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected.Results97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours.ConclusionAlthough a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.

Highlights

Worldwide, bronchiolitis remains one of the most common reasons for hospitalisation of children [1]
Conclusion: a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing length of stay (LOS), duration of O2 requirement or readmissions in children hospitalised with bronchiolitis
One participant was excluded from the analysis of primary outcomes; they had received a macrolide in the previous 7 days

Summary

Introduction

Bronchiolitis remains one of the most common reasons for hospitalisation of children [1]. Over 3 million children are diagnosed with bronchiolitis annually [2,3]. The incidence of bronchiolitis is higher in some populations, including Alaskan Native and Indigenous Northern Territory (NT) infants [1]. In the latter group, hospitalisation rates for bronchiolitis are higher [4] (352 vs 62.6 per 1000) and infections are more severe than nonIndigenous children [5]. Bronchiolitis is a clinical syndrome that is diagnosed in children up to 24 months of age [6,7,8]. The most common infecting virus, respiratory syncytial virus (RSV) occurs in 50–80% of cases, [9] an increasing number of viruses

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Conclusion