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CLINICAL QUESTION Is prophylactic antibiotic treatment associated with fewer exacerbations or improved health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD)? BOTTOM LINE Continuous macrolide antibiotic use for prophylaxis was associated with a clinically significant reduction in COPD exacerbations. Pulsed antibiotic use was not associated with benefit. Continuous and pulsed antibiotics were associated with improved HRQOL, but this was not clinically significant.