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.; 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 hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.; Clinical Trial Registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099.eCollection. Cited Medium: Print. NLM ISO Abbr: Front Pediatr. PubMed Central ID: PMC4404864. Linked References: Antiviral Res. 2009 Aug;83(2):191-200. (PMID: 19463856); Pediatrics. 2010 Aug;126(2):285-90. (PMID: 20624799); J Paediatr Child Health. 2003 Jan-Feb;39(1):40-5. (PMID: 12542811); J Pediatr. 2012 Dec;161(6):1104-8. (PMID: 22748516); Lancet Respir Med. 2013 Oct;1(8):610-20. (PMID: 24461664); J Pediatr. 2010 Dec;157(6):1001-5. (PMID: 20656297); Lancet Infect Dis. 2013 Dec;13(12):1057-98. (PMID: 24252483); Pediatrics. 2014 Nov;134(5):e1474-502. (PMID: 25349312); Pediatr Pulmonol. 2014 Feb;49(2):189-200. (PMID: 23401398); Pediatr Infect Dis J. 2005 May;24(5):423-8. (PMID: 15876941); Epidemiol Infect. 2008 Oct;136(10):1333-41. (PMID: 18177522); Pediatr Pulmonol. 2008 Feb;43(2):142-9. (PMID: 18085694); PLoS One. 2013 Sep 25;8(9):e74316. (PMID: 24086334); Eur Respir J. 2010 Sep;36(3):646-54. (PMID: 20150207); Pediatr Infect Dis J. 1994 Nov;13(11):983-9. (PMID: 7845752); Pediatr Infect Dis J. 2012 Apr;31(4):341-6. (PMID: 22173140); Trials. 2011 Apr 14;12:94. (PMID: 21492416); Int J Antimicrob Agents. 2012 Oct;40(4):365-9. (PMID: 22819151); BMC Public Health. 2014 Jun 18;14:622. (PMID: 24943961); Lancet Infect Dis. 2013 Dec;13(12):1004-5. (PMID: 24252478); Lancet Infect Dis. 2014 Aug;14(8):742-50. (PMID: 25022435); J Paediatr Child Health. 2009 Oct;45(10):593-7. (PMID: 19751375); Pharmacol Ther. 2014 Aug;143(2):225-45. (PMID: 24631273); J Infect Dis. 2014 Aug 15;210(4):585-92. (PMID: 24652498); Curr Opin Pulm Med. 2010 May;16(3):217-25. (PMID: 20375783); J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):294-307. (PMID: 25313849); Arch Dis Child Educ Pract Ed. 2007 Oct;92 (5):ep149-51. (PMID: 17895265); BMJ Open. 2012 Oct 31;2(6):null. (PMID: 23117571); Pediatr Infect Dis J. 2004 Oct;23(10):902-8. (PMID: 15602188); Curr Opin Pediatr. 2014 Jun;26(3):328-33. (PMID: 24739493); Pediatr Pulmonol. 2013 Aug;48(8):772-9. (PMID: 22997178); Lancet. 2010 May 1;375(9725):1545-55. (PMID: 20399493); Eur Respir J. 2007 Jan;29(1):91-7. (PMID: 17050564); PLoS One. 2013 Aug 05;8(8):e70478. (PMID: 23940582). Linking ISSN: 22962360. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2015 Apr 21. ; Original Imprints: Publication: Lausanne : Frontiers Media SA, [2013]- <br />