Efficacy of Antibiotic Therapy for Acute Exacerbations of Mild to Moderate Chronic Obstructive Pulmonary Disease

Rationale Antimicrobial therapy remains a controversial issue in nonsevere exacerbations of chronic obstructive pulmonary disease (COPD). Objectives To evaluate the efficacy of antibiotic therapy in moderate exacerbations of mild-to-moderate COPD. Methods This study involved a multicenter, parallel, double-blind, placebo-controlled, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers of 10 pack-years or more with spirometrically confirmed mild-to-moderate COPD (FEV1 > 50% predicted and FEV1/FVC ratio < 0.7) and diagnosed with an exacerbation were enrolled in the study. The patients were randomized to receive amoxicillin/clavulanate 500/125 mg three times a day or placebo three times a day for 8 days. Measurements and Main Results The primary outcome measure was clinical cure at end of therapy visit (EOT) at Days 9 to 11. A total of 310 subjects fulfilled all the criteria for efficacy analysis. A total of 117 patients with amoxicillin/clavulanate (74.1%) and 91 with placebo (59.9%) were considered cured at EOT (difference, 14.2%; 95% confidence interval, 3.7–24.3). The median time to the next exacerbation was significantly longer in patients receiving antibiotic compared with placebo (233 d [interquartile range, 110–365] compared with 160 d [interquartile range, 66–365]; P < 0.05). The best C-reactive protein serum cut-off for predicting clinical failure with placebo was 40 mg/L, with an area under the curve of 0.732 (95% confidence interval, 0.614–0.851). Conclusions Treatment of ambulatory exacerbations of mild-to-moderate COPD with amoxicillin/clavulanate is more effective and significantly prolongs the time to the next exacerbation compared with placebo. Clinical trial registered with www.clinical.gov (NCT00495586).