Efficacy of Azithromycin in Preventing Pulmonary Exacerbations Among Patients With Bronchiectasis: A Systematic Review and Meta-Analysis

Bronchiectasis is a debilitating chronic respiratory condition characterized by a vicious cycle of infection, inflammation, and airway destruction, leading to frequent pulmonary exacerbations. While long-term macrolide therapy, particularly azithromycin, has been proposed for its antibiotic and anti-inflammatory effects, previous systematic reviews have reported inconsistent findings or failed to include the most recent randomized controlled trials (RCTs). This study aimed to provide a comprehensive, updated meta-analysis of the efficacy and safety of long-term azithromycin in reducing pulmonary exacerbations. We systematically searched PubMed, ClinicalTrials.gov, and the Cochrane Library through December 2025, identifying six RCTs involving 562 patients. The analysis revealed that long-term azithromycin prophylaxis significantly reduced the rate of pulmonary exacerbations compared to placebo, with a pooled standardized mean difference (SMD) of -0.63 (95% CI, -0.90 to -0.35; p < 0.00001). Subgroup analysis demonstrated consistent benefits in both adult (SMD -1.03) and pediatric (SMD -1.52) populations (p = 0.10 for subgroup difference), despite moderate heterogeneity (I² = 58%). While treatment did not yield statistically significant improvements in forced expiratory volume in 1 second (FEV1) predicted (p = 0.08) or St. George's Respiratory Questionnaire (SGRQ) scores (p = 0.81), the incidence of adverse events was comparable to placebo (relative risk (RR) 1.24; 95% CI, 0.95 to 1.61; p = 0.11). These findings indicate that azithromycin is a safe and effective intervention for preventing exacerbations in both children and adults and should be considered in the management of patients with frequent respiratory events.