Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

Abstract

Marjolein Brusse-Keizer,1 Paul VanderValk,2 Rogier W van der Zanden,3 Lars Nijdam,4 Job van der Palen,1,5 Ron Hendrix,6,7 Kris Movig4 1Medical School Twente, 2Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, 3Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, 4Department of Clinical Pharmacy, Medisch Spectrum Twente, 5Department of Research Methodology, Measurement and Data Analysis, University of Twente, 6Regional Laboratory of Public Health, Enschede, 7Department of Medical Microbiology, University Medical Centre Groningen, and University of Groningen, Groningen, the Netherlands Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90.Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum.Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95% confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78% of sputum samples and in 30% of serum samples.Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.Keywords: chronic obstructive pulmonary disease, exacerbation, amoxicillin, clavulanic acid, MIC90, concentration