title: Inhibitor resistant class A beta-lactamases.
abstract: Beta-lactamase inhibitors (clavulanic acid, tazobactam, and sulbactam) greatly enhance the therapeutic efficacy of their partner antibiotics (amoxacillin, ampicillin, piperacillin, and ticarcillin) against common enteric and non-enteric organisms possessing class A beta-lactamases. Unfortunately, the number of class A enzymes being discovered that are resistant to these combinations is increasingly rapidly. The TEM and SHV class A beta-lactamases resistant to inhibitors have point mutations in critical amino acids important for catalysis. Compared to the wild type beta-lactamase, inhibitor resistant enzymes are inefficient at hydrolyzing benzylpenicillin, aminopenicillins, and cephalosporins. Nevertheless, hyper-production of these enzymes resulting from mutations in the promoter region can confer substantial levels of resistance. Understanding the microbiologic and kinetic properties of these inhibitor resistant class A beta-lactamases can lead to the design of more potent beta-lactam compounds as well as more effective inhibitors.
authors.affiliation: Geriatric CARE Center, Cleveland, OH 44120, USA. rab14@po.cwru.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: L B
authors.initials: LB
authors.lastname: Rice
mesh_terms: D019943:Amino Acid Substitution; D002511:Cephalosporins / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000145:classification / Q000235:genetics / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases