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, double‐dummy, 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 amoxicillin‐clavulanate 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.