Abstract
Pharmacokinetic–pharmacodynamic (PK–PD) modelling was used to study the impact of the pharmacokinetics of tazobactam on the antimicrobial effect of piperacillin–tazobactam combinations. An in vitro experiment using a novel dilution system was performed to compare the effects of two conditions of the combination therapy against Escherichia coli ATCC35218, a β-lactamase producing bacterium. Both conditions simulated the same initial concentrations of piperacillin and tazobactam, but different elimination half-lives for tazobactam. The killing and regrowth kinetics of E. coli clearly indicated that there is a difference in the antimicrobial effects when there is a difference in the pharmacokinetics of tazobactam in the combination therapy. The results show that for equal piperacillin exposure, different tazobactam half-lives will have a significant effect on antimicrobial outcome.
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