AN INVITRO AND INVIVO COMPARISON OF THE ACTIVITY OF BETA-LACTAMASE INHIBITOR COMBINATIONS WITH IMIPENEM AND CEPHALOSPORINS AGAINST ESCHERICHIA-COLI PRODUCING TEM-1 OR TEM-2 BETA-LACTAMASE

Reference strains of Escherichia coil (ampicillin-susceptible and -resistant ATCC strains, and known TEM-1 and TEM-2 β-lactamase producers) were tested in vitro and in the in-vivo mouse thigh infection model against four β-lactamase inhibitor compounds (BICs: amoxycillin/clavulanic acid, ampicillin/sulbactam, ticarcillin/ clavulanic acid, and piperacillin/tazobactam), selected cephalosporins, and imipenem. The ATCC strains (ampicillin-susceptible and -resistant) were susceptible to the BICs in disc and MIC tests. Three or more logs of killing were observed at the NCCLS breakpoint concentrations. However, the TEM-1 and TEM-2 producers were resistant in disc tests to ampicillin/sulbactam and amoxycillin/clavulanic acid, and showed intermediate susceptibility to ticarcillin/clavulanic acid. MICs were at or near the breakpoint, but bactericidal activity was only noted at the probable breakpoint concentration of piperacillin/tazobactam. Cefoxitin, cefotaxime, cefpirome and imipenem, but not cephalothin, showed greater bactericidal activity and lower MICS for the TEM-producing strains than the BICs. The viable count of the TEM-1 producer was not reduced in the mouse thigh model by ampicillin/ sulbactam or amoxycillin/clavulanic acid, but cefpirome and cefotaxirne reduced the viable count by approximately three logs. There was a 50% mortality rate in mice receiving the two BICs. The ampicillin-susceptible ATCC strain of E. coil was killed to a similar degree by all agents tested. Overall, the BICs appeared inferior, in both in-vivo and in-vitro tests to selected cephalosporins and imipenem when tested against reference strains of E. coil producing TEM-1 or TEM-2 β-lactamase. The large inoculum effect and poor bactericidal activity observed with the BICs suggest they could be less effective in certain clinical situations. © 1991, by The British Society for Antimicrobial Chemotherapy.