Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2012 Oct 15;186(8):716-23. doi: 10.1164/rccm.201206-0996OC. Epub 2012 Aug 23.


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 (FEV(1) > 50% predicted and FEV(1)/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.

Trial registration: ClinicalTrials.gov NCT00495586.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*


  • Anti-Bacterial Agents
  • Biomarkers
  • Amoxicillin-Potassium Clavulanate Combination
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00495586