Azithromycin and amoxicillin-clavulanate are equally effective for resolving nonsevere bronchiectasis in children, although exacerbations were significantly shorter in duration for patients taking amoxicillin-clavulanate, and adverse events were less prevalent in patients taking azithromycin, according to a study published in The Lancet.
Researchers conducted this randomized, double-blind, double-dummy, parallel-group, noninferiority, controlled trial between April 2012 and August 2016 in 1 hospital in New Zealand and 3 in Australia. The cohort included 179 children aged 1 to 19 years with radiographically proven bronchiectasis not related to cystic fibrosis, who were randomly assigned to take an oral suspension of azithromycin (5 mg/kg per day) and placebo (n=82) or amoxicillin-clavulanate (22.5 mg/kg, twice daily) and placebo (n=97) for 21 days. The primary outcome was exacerbation resolution (return to baseline) by 21 days, but various secondary outcomes were also assessed, including exacerbation duration and time to next exacerbation.
By day 21 of the study, 84% (n=61) of the 73 exacerbations in the azithromycin group had resolved compared with 84% (n=73) of the 87 exacerbations in the amoxicillin-clavulanate group. This risk difference confirmed the noninferiority hypothesized by study investigators (risk difference -0.3%, 95% CI, -11.8 to 11.1).
Exacerbations were longer in duration for the azithromycin group than in the amoxicillin-clavulanate group (median 14 days [interquartile range (IQR) 8-16] vs 10 days [IQR 6-15]; P=.014), and adverse events that could be attributed to the study medication were seen in 24% (23 of 97) of the amoxicillin-clavulanate group vs 21% (17 of 82) of the azithromycin group (relative risk 0.9; 95% CI, 0.5-1.5).
Study investigators concluded that, “[a]zithromycin should therefore be regarded only as an alternative treatment for bronchiectasis exacerbations in children with penicillin hypersensitivity or if there is a high-risk of poor adherence with multiple daily dosing and directly observed therapy is possible… until [further] data are available, amoxicillin–clavulanate remains the empirical first-line therapy of choice for treating nonsevere exacerbations of bronchiectasis in children.”
Goyal V, Grimwood K, Byrnes CA, et al. Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet. 2018;392(10154):1197-1206.