Meta-analysis of macrolide maintenance therapy for prevention of disease exacerbations in patients with noncystic fibrosis bronchiectasis

BACKGROUND: Macrolide maintenance treatment remains controversial for patients with noncystic fibrosis (non-CF) bronchiectasis, we performed a meta-analysis to estimate the benefits and safety of macrolides therapy in adults and children with non-CF bronchiectasis. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science databases were searched for all the randomized controlled trials of macrolides for treating non-CF bronchiectasis. The primary outcome was improvement of bronchiectasis exacerbations. Secondary outcomes included adverse events and macrolide resistance. RESULTS: A total of 10 studies involving 602 patients were included in the analysis. Pooled results showed that macrolide therapy significantly reduced the number of patients who suffered from exacerbations (RR = 1.56, 95% CI = 1.14–2.14, P = .006, I(2) = 72%), number of patients who experienced at least 3 exacerbations (RR = 0.55, 95% CI = 0.39–0.77, P = .0005, I(2) = 40%), average exacerbations per patient during the observation time (SMD = −0.69, 95% CI = −1.06 to −0.32, P = .0002, I(2) = 60%), and bronchiectasis exacerbation-related admissions (RR = 0.46, 95% CI = 0.23–0.96, P = .04, I(2) = 0%). Specified subgroup analyses of the number of patients free from exacerbations were further performed; macrolide therapy showed a significant benefit in both children (RR 5.03, 95% CI 2.02–12.50, P = .0005, I(2) = 45%) and adults (RR = 1.66, 95% CI = 1.37–2.02, P < .00001, I(2) = 79%); azithromycin showed a significant reduction on the number of patients who suffered from exacerbations (RR = 2.25, 95% CI = 1.67–3.02, P < .00001, I(2) = 0%), was different from erythromycin (RR = 1.33, 95% CI = 0.92–1.94, P = .13, I(2) = 0%) and roxithromycin (RR = 1.14, 95% CI = 0.97–1.35, P = .11, I(2) = 0%). The pooled results also showed no higher risk of adverse events (RR = 0.98, 95% CI = 0.85–1.13, P = .80, I(2) = 8%), even a lower risk of severe adverse events (RR = 0.53, 95% CI = 0.33–0.85, P = .009, I(2) = 0%). However, a higher risk of macrolide resistance (RR = 3.59, 95% CI 2.6–4.96, P < .00001, I(2) = 0%) was observed. CONCLUSION: For both children and adults with non-CF bronchiectasis, macrolide maintenance therapy can effectively reduce bronchiectasis exacerbations, especially for patients with more frequent exacerbations and needing hospital treatment. Azithromycin was more effective than other macrolides. Macrolide maintenance therapy did not increase the risk of adverse events, but may increase the risk of macrolide resistance.