The effectiveness of macrolide antibiotics in non-cystic bronchiectasis: Cochrane systematic review

Background Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways1. It is estimated that global prevalence in adults will increase from approximately 2.4 million in 2012 to over 3 million by 20202 . In the UK, the incidence and prevalence of bronchiectasis is higher than previously estimated3. This Cochrane systematic review of macrolide therapy is the first of a series of five systematic reviews of antibiotics for bronchiectasis, designed to address gaps in the evidence base in terms of the safety and effectiveness of therapy 4,5. Objective To determine the impact of macrolide antibiotics in the treatment of adults and children with non-cystic fibrosis bronchiectasis. Methods Participants Adults and children Diagnosed with bronchiectasis by bronchography, plain film chest radiograph, or high resolution computed tomography Intervention Macrolide antibiotics versus placebo or standard care or non-macrolide antibiotics Minimum four weeks duration Study design Randomised controlled trials (RCTs), including those using a cross-over design Outcomes Primary: exacerbations, hospitalisations, and serious adverse events Secondary: sputum volume and purulence; pulmonary function tests; systemic markers of infection; adverse events, mortality; antibiotic resistance; exercise capacity; and health related quality of life. Search Methods for Identification of Studies Electronic Searches: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), AMED (Allied and Complementary Medicine), and PsycINFO Hand searches: core respiratory conference abstracts (e.g. American Thoracic Society (ATS); European Respiratory Society (ERS)) Trial registries Reference lists Protocol (http://onlinelibrary.wiley.com/ doi/10.1002/14651858.CD012406/ full) Results We included 16 studies; 679 adults (12 studies), and 179 children (4 studies) (Figures 1,2) 15 RCTs, and 1 cross-over design Adults Moderate quality evidence (GRADE criteria) that macrolide, particularly azithromycin, may reduce the frequency of exacerbations (odds ratio 0.34, 95% CI 0.21 to 0.53; I2 = 49%) and improve quality of life among adults with bronchiectasis (mean difference -5.29, 95% CI -8.83 to -1.74; I2 = 43%) (Figure 3, Table 1). Low quality evidence that azithromycin may increase the antimicrobial resistance (OR 1.09, 95% CI 0.22 to 5.39; participants = 200; studies = 4; I2 = 33%) Children Moderate quality evidence that macrolide particularly azithromycin, may reduce the frequency of exacerbations (OR 0.40, 95% CI 0.11 to 1.41; participants = 89) based on one study Low quality evidence that azithromycin may increase the antimicrobial resistance (OR 7.31, 95% CI 2.23 to 23.92; participants = 89; studies = 1; I2 = 0%) Conclusion Long term macrolide therapy may reduce exacerbation rate and improve healthrelated quality of life of patients with bronchiectasis. The supporting evidence for this recommendation is derived mainly from studies of azithromycin and in predominantly adults rather than children. There is a need for further trials to determine the impact of long-term macrolide antibiotics in the treatment of adults and children with bronchiectasi