title: Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease.
abstract: 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 <LMIC90 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical School Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Brusse-Keizer
authors.affiliation: Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: VanderValk
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: van der Zanden
authors.affiliation: Department of Clinical Pharmacy, Medisch Spectrum Twente, the Netherlands.
authors.forename: Lars
authors.initials: L
authors.lastname: Nijdam
authors.affiliation: Medical School Twente, Medisch Spectrum Twente, Enschede, the Netherlands ; Department of Research Methodology, Measurement and Data Analysis, University of Twente, the Netherlands.
authors.forename: Job
authors.initials: J
authors.lastname: van der Palen
authors.affiliation: Regional Laboratory of Public Health, Enschede, the Netherlands ; Department of Medical Microbiology, University Medical Centre Groningen, and University of Groningen, Groningen, the Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Hendrix
authors.affiliation: Department of Clinical Pharmacy, Medisch Spectrum Twente, the Netherlands.
authors.forename: Kris
authors.initials: K
authors.lastname: Movig
mesh_terms: D000368:Aged; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000378:metabolism / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018450:Disease Progression; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D013183:Sputum / Q000201:enzymology*; D001618:beta-Lactamases / Q000032:analysis*
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; D001618:beta-Lactamases
keywords: MIC90; amoxicillin; chronic obstructive pulmonary disease; clavulanic acid; concentration; exacerbation