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. Nasopha-ryngeal 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, respira-tory 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 difference0.4bacteria/child,95%CI:0.2,0.6; p<0.001), buthadno significant effectuponvirusdetectionrates. Conclusion: Despite reducingnasopharyngealbacterialcarriage,threelargeonce- weekly dosesofazithromycindidnotconferanybenefitoverplaceboduringthe bronchiolitisillnessor6monthsposthospitalization.Azithromycinshouldnotbeused routinelytotreatinfantshospitalizedwithbronchiolitis.