AUTHOR=McCallum Gabrielle B. , Morris Peter S. , Grimwood Keith , Maclennan Carolyn , White Andrew V. , Chatfield Mark D. , Sloots Theo P. , Mackay Ian M. , Smith-Vaughan Heidi , McKay Clare C. , Versteegh Lesley A. , Jacobsen Nerida , Mobberley Charmaine , Byrnes Catherine A. , Chang Anne B. 

TITLE=Three-Weekly Doses of Azithromycin for Indigenous Infants Hospitalized with Bronchiolitis: A Multicentre, Randomized, Placebo-Controlled Trial

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 3 - 2015

YEAR=2015

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2015.00032

DOI=10.3389/fped.2015.00032

ISSN=2296-2360

ABSTRACT=Background 
Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3-weeks of azithromycin improve clinical outcomes beyond the hospitalisation period. In an international, double-blind randomised controlled trial, we determined if 3-weeks of azithromycin, improved clinical outcomes in Indigenous infants hospitalised with bronchiolitis. 

Methods 
Infants aged ≤24-months were enrolled from three centres and randomised to receive three once-weekly doses of either azithromycin (30mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48-hours later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12-hours until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalisations within 6-months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48-hours. 

Results 
Two-hundred-and-nineteen infants were randomised (n=106 azithromycin, n=113 placebo). No significant between-group differences were found for LOS (median 54-hours for each group, difference=0-hours, 95%CI: -6, 8; p=0.8), time receiving oxygen (azithromycin=40-hours, placebo=35-hours, group difference=5-hours, 95%CI: -8, 11; p=0.7), day-21 symptom/signs or rehospitalisation within 6-months (azithromycin n=31, placebo=25 infants, p=0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95%CI: 0.2, 0.6; p<0.001), but had no significant effect upon virus detection rates. 
 
Conclusion
Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6-months post-hospitalisation. Azithromycin should not be used routinely to treat infants hospitalised with bronchiolitis. 

Clinical trial registration 
The trial was registered with the Australian and New Z