Oral antibiotics vs placebo for exacerbations of paediatric bronchiectasis

Abstract

Background: Bronchiectasis guidelines recommend antibiotics for treating acute respiratory exacerbations, but no RCTs of antibiotics vs placebo exist. Aim: We hypothesized that oral amoxicillin-clavulanate (amox-clav) and azithromycin (azitho) are both superior to placebo for achieving resolution by day-14 when treating non-severe exacerbations in children. Methods: Our multicentre (n=4), double-dummy, double-blind, placebo-controlled trial randomized children aged 1-19 years at exacerbation start to amox-clav (45mg/kg/day) + azithro-placebo; azithro (5mg/kg/day) + amox-clav-placebo; or placebo + placebo for 14-days. The primary outcome was exacerbation resolution by day-14. Secondary outcomes were exacerbation duration, time-to-next exacerbation, quality-of-life, laboratory and FEV1 assessments and nasopharyngeal microbiology. Statistical significance was set at P<0.0245. Results: 197 children were randomized (amox-clav n=63, azithro n=67, placebo n=67). By day-14, exacerbations resolved in 41 (65%), 41 (61%) and 29 (43%) children in the respective groups. Compared to placebo, the relative risk of resolution by day-14 for amox-clav was 1.50 (95% confidence interval [CI] 1.08-2.09; P=0.02, number needed-to-treat for benefit=5, 95%CI 3-20) and for azithro 1.41 (95%CI 1.01-1.97; P=0.04). Compared to placebo, the median exacerbation duration was significantly shorter for amox-clav (7 vs. 10-days, P=0.02), but not for azithro (8 vs 10-days, P=0.24). Other secondary between-group outcomes were not significantly different. Respiratory viruses were identified in 53% of exacerbations. Conclusion: Oral amox-clav, but not azithro is superior to placebo for treating non-severe bronchiectasis exacerbations in children.