title: Three-weekly doses of azithromycin for indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial.
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 hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.
  
  
  METHODS
  Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.
  
  
  RESULTS
  Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: -6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: -8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 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.
  
  
  CONCLUSIONS
  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 hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.
  
  
  BACKGROUND
  The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099.
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia.
authors.forename: Gabrielle B
authors.initials: GB
authors.lastname: McCallum
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia ; Department of Paediatrics, Royal Darwin Hospital , Darwin, NT , Australia.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Morris
authors.affiliation: Menzies Health Institute Queensland, Griffith University and Gold Coast University Hospital , Gold Coast, QLD , Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Grimwood
authors.affiliation: Department of Paediatrics, Royal Darwin Hospital , Darwin, NT , Australia.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Maclennan
authors.affiliation: Department of Paediatrics, Townsville Hospital , Townsville, QLD , Australia.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: White
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Chatfield
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Sir Albert Sakzewski Virus Research Centre, Children's Health Queensland Hospital and Health Service, University of Queensland , Herston, QLD , Australia.
authors.forename: Theo P
authors.initials: TP
authors.lastname: Sloots
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Sir Albert Sakzewski Virus Research Centre, Children's Health Queensland Hospital and Health Service, University of Queensland , Herston, QLD , Australia ; Clinical Medical Virology Centre, School of Chemistry and Molecular Biosciences, University of Queensland , St Lucia, QLD , Australia.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Mackay
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Smith-Vaughan
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia.
authors.forename: Clare C
authors.initials: CC
authors.lastname: McKay
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Versteegh
authors.affiliation: Department of Paediatrics, Townsville Hospital , Townsville, QLD , Australia.
authors.forename: Nerida
authors.initials: N
authors.lastname: Jacobsen
authors.affiliation: The University of Auckland and Starship Children's Hospital , Auckland , New Zealand.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Mobberley
authors.affiliation: The University of Auckland and Starship Children's Hospital , Auckland , New Zealand.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Byrnes
authors.affiliation: Child Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia ; Queensland Children's Medical Research Institute, Children's Health Queensland, Queensland University of Technology , Brisbane, QLD , Australia.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
keywords: Indigenous; azithromycin; bacteria; bronchiolitis; macrolides; randomized controlled trial; respiratory syncytial virus; viruses