Efficacy of oral antibiotics for non-severeexacerbations of bronchiectasis in children

Abstract

Introduction: Antibiotics are used routinely to treat bronchiectasis exacerbations. However, placebo-containing RCTs are lacking and, in non-severe (non-hospitalised) cases, antibiotics might be unnecessary since many exacerbations are virus-triggered. We tested our primary hypothesis that when treating a non-severe exacerbation in children with bronchiectasis, oral amoxicillin-clavulanate and azithromycin are superior to placebo for achieving resolution by day-14. Methods: We conducted a multicentre, parallel-group, doubledummy, double-blind placebo-controlled RCT in 4 centres. When an exacerbation began, children were randomised to receive either amoxicillin-clavulanate (22.5 mg/kg bd)/placebo, azithromycin (5 mg/kg/day)/placebo or placebo/placebo for 14-days. Our primary outcome was exacerbation resolution (defined as 'return-to-baseline') by 14-days. Secondary outcomes were exacerbation duration, time-to-next exacerbation, cough-specific quality-of-life (PC-QoL), white blood cell count and CRP and FEV1. Nasal swabs were also collected. Results: One-hundred-and-ninety-seven children were randomised (amoxicillin-clavulanate n = 63, azithromycin n = 67, and placebo n = 67). Their baseline characteristics were comparable. By day-14, exacerbations had resolved in 41/63, 41/67 and 29/67 of the 3 groups respectively. Compared to placebo, the relative-risk-of-resolution by day-14 was 1.50 (95% CI 1.08-2.09; number-needed-to-treat for benefit (NNTFB = 5, 95%CI 3-21) and 1.41 (95% CI 1.01-1.97; NNTFB = 6, 95% CI 3-97) in the amoxicillin-clavulanate and azithromycin groups respectively. The median exacerbation duration was significantly shorter in the amoxicillinclavulanate group (7 vs 10-days, P = 0.018) than placebo, but not for azithromycin (8 vs 10-days P = 0.242). There were no significant differences in time-to-next exacerbation, or changes in PC-QoL, white blood cell count, CRP or FEV1% between treatment days 1-14 in either active arm compared to placebo. At exacerbation onset, 57% of nasal swabs contained a respiratory virus. Conclusion: Amoxicillin-clavulanate and azithromycin are both superior to placebo for treating non-severe exacerbations of bronchiectasis in children without Pseudomonas aeruginosa. Identifying those most likely to benefit from antibiotics is now a priority.L6269397602019-04-02 <br />