Impact of tazobactam pharmacokinetics on the antimicrobial effect of piperacillin-tazobactam combinations.
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 beta-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.
Liu
Q
Q
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
Rand
K
K
Derendorf
H
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008433:Mathematics; D008954:Models, Biological; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D000078142:Tazobactam; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam; D010878:Piperacillin