title: Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations.
abstract: Recent reports that members of the family Enterobacteriaceae that produce high levels of certain beta-lactamases are often resistant to ticarcillin-clavulanate prompted this study to assess the relationship between type and amount of enzyme produced and susceptibility to ticarcillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Agar dilution MICs were determined by using 73 strains of Enterobacteriaceae that produced a single beta-lactamase that had been characterized and quantified and a beta-lactamase-negative control strain of Escherichia coli. For E. coli and Klebsiella pneumoniae, MICs of each combination increased as levels of TEM, SHV-1, or class IV enzymes increased. However, the percentage of strains that were resistant was highest for ticarcillin-clavulanate (32%), with only 18 and 6% resistant to piperacillin-tazobactam and cefoperazone-sulbactam, respectively. Strains producing PSE-1, regardless of level, were resistant or moderately susceptible to ticarcillin-clavulanate but were susceptible to piperacillin-tazobactam and cefoperazone-sulbactam. HMS-1 and OHIO-1 beta-lactamases were associated with resistance to ticarcillin-clavulanate and piperacillin-tazobactam, respectively. High levels of class IV enzymes in Klebsiella oxytoca were associated with resistance to all three combinations. These results indicate that the level and type of beta-lactamase produced by members of the family Enterobacteriaceae are important determinants of susceptibility to beta-lactam-inhibitor combinations, especially ticarcillin-clavulanate.
authors.affiliation: Department of Medical Microbiology, Creighton University School of Medicine, Omaha, Nebraska 68178.
authors.forename: K S
authors.initials: KS
authors.lastname: Thomson
authors.forename: D A
authors.initials: DA
authors.lastname: Weber
authors.forename: C C
authors.initials: CC
authors.lastname: Sanders
authors.forename: W E
authors.initials: WE
authors.lastname: Sanders
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002438:Cefoperazone / Q000494:pharmacology*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D013407:Sulbactam / Q000494:pharmacology*; D013982:Ticarcillin / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D004338:Drug Combinations; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D002438:Cefoperazone; D001618:beta-Lactamases; D013982:Ticarcillin; D013407:Sulbactam; D010878:Piperacillin