title: Susceptibility of Escherichia coli isolates with TEM-1 beta-lactamase to combinations of BRL42715, tazobactam or clavulanate with piperacillin or amoxycillin .
abstract: Production of TEM-1 beta-lactamase is the commonest cause of acquired resistance to amoxycillin and piperacillin in Escherichia coli, now occurring in c. 50% of isolates. Consecutive E. coli isolates producing TEM-1 beta-lactamase were collected at The London Hospital in 1982 (n = 50) and 1989 (n = 46). Enzyme quantities varied 150-fold amongst the isolates. Randomly-selected isolates from both years (n = 36; nine per quartile of the beta-lactamase activity distribution) were tested for susceptibility to combinations of amoxycillin or piperacillin with clavulanate or tazobactam or with BRL42715, a novel penem. The inhibitor concentrations needed to potentiate the penicillins related to the amount of beta-lactamase produced. BRL42715, at 1 mg/l, rendered all the isolates, including TEM-1 hyperproducers, susceptible to the recommended BSAC breakpoints of 8 mg amoxycillin/1 and 16 mg piperacillin/l. At 2 mg/l, BRL42715 almost always reduced amoxycillin and piperacillin MICs to the levels (1-2 mg/l) expected for E. coli isolates that lack TEM-1 enzyme. Tazobactam, at 1-2 mg/l, reduced piperacillin MICs to 1-2 mg/l for strains in the lower half of the beta-lactamase distribution, but greater than 8 mg tazobactam/l was required to reduce piperacillin MICs to 16 mg/l for one-third of the top quartile isolates. Clavulanate was a stronger potentiator of piperacillin than was tazobactam. On the other hand, amoxycillin was a more difficult substrate to potentiate than piperacillin, and isolates with enzyme levels in the top half of the distribution generally required greater than or equal to 8 mg clavulanate/l to reduce amoxycillin MICs to less than or equal to 8 mg/l.
authors.affiliation: Department of Medical Microbiology, London Hospital Medical College, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: P
authors.initials: P
authors.lastname: Seetulsingh
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D007769:Lactams; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology; D000078142:Tazobactam; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D007769:Lactams; D047090:beta-Lactams; C061593:C6-(N1-methyl-1,2,3-trazolylmethylene)penem; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D010397:Penicillanic Acid; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D000078142:Tazobactam; D010878:Piperacillin