Pharmacokinetics-pharmacodynamics of β-lactamase inhibitors: are we missing the target?

Marguerite L. Monogue, David P. Nicolau

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

Introduction: β-lactamase production in Gram-negative bacteria is a leading cause of antimicrobial resistance. β-lactamase inhibitors are therapeutic agents used in combination with a partner antimicrobial to overcome the production of these enzymes and restore antimicrobial activity. To address the ongoing threat of multi-drug resistant bacteria, a recent wave of β-lactamase inhibitor development has occurred. Emphasis on the pharmacokinetics and pharmacodynamics of these agents is needed to optimize their clinical impact. Areas covered: This review will describe methods currently used to define the pharmacokinetics/pharmacodynamics of β-lactamase inhibitors. Minimal focus will be on the structure and mechanism of β-lactamase inhibitors. Emphasis will be placed on the use of specific thresholds to normalize β-lactamase inhibitor exposure. In vitro and in vivo pharmacokinetic/pharmacodynamic data specific to FDA approved and pipeline β-lactamase inhibitors will be explored. Expert opinion: Describing the exposure-response relationship of β-lactamase inhibitors is an ongoing challenge due to the dynamic relationship of the β-lactamase inhibitor with the active partner compound. Pharmacokinetic/pharmacodynamic indices and target exposures lack generalizability, as they are often specific to the infecting organism and/or β-lactamase, rather than β-lactamase inhibitor class. Selected dosage regimens of new agents should be validated via the use of population target attainment analyses.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalExpert Review of Anti-Infective Therapy
Volume17
Issue number8
DOIs
StatePublished - Jan 1 2019

Keywords

  • Antimicrobials
  • multi-drug resistance
  • pharmacodynamics
  • pharmacokinetics
  • β-lactamases

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Virology
  • Infectious Diseases

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