Combination Antibiotic Therapy Versus Monotherapy in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: an Open-label Randomized Trial

Background: The role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD.

Methods: We enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated.

Results: Clinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05).

Conclusions: Concomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.