SUSCEPTIBILITY OF ESCHERICHIA-COLI ISOLATES WITH TEM-1 BETA-LACTAMASE TO COMBINATIONS OF BRL42715, TAZOBACTAM OR CLAVULANATE WITH PIPERACILLIN OR AMOXICILLIN

Production of TEM-1 β-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 β-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 β-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 poten tiate the penicillins related to the amount of β-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-l enzyme. Tazobactam, at 1-2 mg/l, reduced piperacillin MICs to 1-2 mg/l for strains in the lower half of the β-lactamase distribution, but > 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 {succeeds or equal to} 8 mg clavulanate/l to reduce amoxycillin MICs to ≤ 8 mg/l. © 1991 The British Society for Antimicrobial Chemotherapy.