Safety and efficacy of Azithromycin in prevention of chronic obstructive pulmonary disease exacerbation: systematic review and meta-analysis

Background: Chronic obstructive pulmonary disease (COPD) causes a major burden in terms of deaths and hospitalizations worldwide; it is associated with progressive lung function loss, and frequent exacerbations. Administration of macrolides has been considered beneficial in reducing the frequency of COPD exacerbations. The aim of this study is to assess the safety and efficacy of long-term administration of Azithromycin for patients with chronic obstructive pulmonary disease. Methods: An extensive search was conducted on SCOPUS, and PubMed databases, CENTRAL, and ClinicalTrials.gov clinical trial registers for randomized clinical trials conducted on COPD patients and administered Azithromycin for more than two weeks. The selected studies underwent assessment for the risk of bias. We conducted random-effect model meta-analysis for the frequency of acute exacerbations during follow-up as a primary outcome. Results: Out of 1021 screened records, 3 RCTs (Randomized controlled trials) involving 1264 patients were included in the final analysis. The pooled data of all 3 trials showed that administration of Azithromycin reduced the frequency of acute exacerbation of COPD [risk ratio (RR) = 0.69; 95% CI 0.53, 0.91, p = 0.01]. Subgroup analysis indicated that 500 mg Azithromycin [risk ratio (RR) =0.65; 95% CI 0.53-0.79, p=0.01] was found to be more beneficial than 250 mg Azithromycin [risk ratio (RR) = 0.60; 95% CI 0.27-1.33, p=0.21] in reducing acute exacerbation rate, however due to many limitations the analysis of the dosage was not conclusive. Conclusion: Long-term Azithromycin administration for COPD patients is statistically not associated with increased risk of developing adverse events; in addition, it might be effective in reducing the frequency of acute exacerbations of COPD. However, dosage and duration of Azithromycin administration analysis was not conclusive and thus more RCTs are needed in these areas.