Pharmacokinetics and Pharmacodynamics of Beta-lactamase Inhibitors.

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Pharmacokinetics and Pharmacodynamics of Beta-lactamase Inhibitors.

Pharmacotherapy. 2018 Dec 27;:

Authors: Crass RL, Pai MP

Novel beta-lactamase inhibitors have extended the reach of new and existing beta-lactams against multi-drug resistant bacteria expressing beta-lactamases. The efficacy of these combination therapeutics is reliant on a complex two-component pharmacodynamic system where the beta-lactamase inhibitor inactivates the bacterial beta-lactamase enzyme and frees the companion beta-lactam to act against its penicillin binding protein target. Despite considerable investigation into the pharmacokinetics/pharmacodynamics of beta-lactams, the pharmacology of their companion beta-lactamase inhibitors has only recently been rigorously explored. This review describes the diversity of beta-lactamase enzymes, mechanisms of enzyme inhibition, and factors impacting the efficacy of clinically available beta-lactamase inhibitors. Relevant pharmacokinetic differences among available inhibitors and the pharmacokinetic/pharmacodynamic properties of these agents are described independently of their companion beta-lactams. In the modern era of antibiotic resistance, a comprehensive understanding of the pharmacology, pharmacokinetics, and pharmacodynamics of beta-lactamase inhibitors is paramount to maximizing the therapeutic efficacy of existing beta-lactam/beta-lactamase inhibitor combinations and protecting novel agents in the drug development pipeline. This article is protected by copyright. All rights reserved.

PMID: 30589457 [PubMed - as supplied by publisher]

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