title: Exploring the effectiveness of tazobactam against ceftazidime resistant Escherichia coli: insights from the comparison between susceptibility testing and beta-lactamase inhibition.
abstract: Thirteen clinical isolates of Escherichia coli resistant to ceftazidime that possessed an AmpC and other (beta-lactamases were identified. The effectiveness of different formulations of piperacillin/tazobactam to other beta-lactams was compared. Antibiotic susceptibility testing, polymerase chain reaction, amplification of blaTEM, blaSHV and blaAmpC, and enzyme-linked immunosorbent assays to identify AmpC beta-lactamases were performed. Hydrolysis rates were obtained and residual enzymatic activity was determined. Cefepime and ertapenem were more active than piperacillin/tazobactam. In contrast, increasing the relative proportion of tazobactam improved susceptibility testing. Twenty micromolar tazobactam inhibited total beta-lactamase activity (as measured by nitrocefin hydrolysis rates) by greater than 75% against all isolates tested: in 11 of 13 E. coli isolates, total beta-lactamase activity was inhibited by 90%. The observed differences between MIC determinations and susceptibility to enzymatic inactivation by tazobactam against E. coli containing AmpC and other -lactamases may be due to the final tazobactam concentration achieved in the periplasmic space. Factors determining this are critical considerations in assessing beta-lactamase inhibitor potency.
authors.affiliation: Infectious Diseases Section, Geriatrics and Extended Care, Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bethel
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Hujer
authors.forename: Marion S
authors.initials: MS
authors.lastname: Helfand
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D000077723:Cefepime; D002442:Ceftazidime / Q000494:pharmacology*; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology; D007769:Lactams; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D007769:Lactams; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000077723:Cefepime; D010397:Penicillanic Acid; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C021720:nitrocefin; D000077727:Ertapenem; D000078142:Tazobactam