Abstract
Thirteen clinical isolates of Escherichia coli resistant to ceftazidime that possessed an AmpC and other (β-lactamases were identified. The effectiveness of different formulations of piperacillin/tazobactam to other β-lactams was compared. Antibiotic susceptibility testing, polymerase chain reaction, amplification of bla TEM, bla SHV and bla AmpC, and enzyme-linked immunosorbent assays to identify AmpC β-lactamases were performed. Hydrolysis rates were obtained and residual enzymatic activity was determined. Cefepime and ertapenem were more active than piperacillin/tazobactam. In contrast, increasing the relative proportion of tazobactam improved susceptibility testing. Twenty micromolar tazobactam inhibited total β-lactamase activity (as measured by nitrocefin hydrolysis rates) by greater than 75% against all isolates tested: in 11 of 13 E. coli isolates, total β-lactamase activity was inhibited by 90%. The observed differences between MIC determinations and susceptibility to enzymatic inactivation by tazobactam against E. coli containing AmpC and other β-lactamases may be due to the final tazobactam concentration achieved in the periplasmic space. Factors determining this are critical considerations in assessing β-lactamase inhibitor potency.
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