title: The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.
abstract: Although there are reports that the addition of a beta-lactamase inhibitor to ampicillin or amoxicillin greatly improves their in vitro activity against M. tuberculosis, there are no written reports about the antituberculosis effects of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis. In this report, we have determined the minimal inhibitory concentrations (MIC) of 5 cephalosporins with or without combination with beta-lactamase inhibitor against M. tuberculosis strains isolated from patients before antituberculosis treatment and checked the production of beta-lactamase by bacteria before this procedure. Four strains of M. tuberculosis were contaminated during the experiment, and all the other 16 strains hydrolyzed the nitrocefin disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400 micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600 micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After adding the equimolar concentrations of sulbactam, the MICs were reduced to 100-200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400 micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800 micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the antituberculosis effect of cephalosporins.
authors.affiliation: Department of Chest Medicine, Veterans General Hospital-Taipei, Taiwan, Republic of China.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: M H
authors.initials: MH
authors.lastname: Yang
authors.forename: J S
authors.initials: JS
authors.lastname: Lin
authors.forename: Y C
authors.initials: YC
authors.lastname: Lee
authors.forename: R P
authors.initials: RP
authors.lastname: Perng
mesh_terms: D002435:Cefamandole / Q000031:analogs & derivatives / Q000494:pharmacology; D002439:Cefotaxime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D002514:Cephapirin / Q000494:pharmacology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013407:Sulbactam / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
chemical_list: D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D002435:Cefamandole; D002443:Ceftriaxone; D002514:Cephapirin; C012653:ceforanide; D002439:Cefotaxime; D013407:Sulbactam