Human-Simulated Antimicrobial Regimens in Animal Models: Transparency and Validation Are Imperative

Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00594-20. doi: 10.1128/AAC.00594-20. Print 2020 Jul 22.

Abstract

Animal infection models are invaluable in optimizing antimicrobial dosage in humans. Utilization of human-simulated regimens (HSRs) in animal models helps to evaluate antimicrobial efficacy at clinically achievable drug concentrations. To that end, pharmacokinetic studies in infected animals and confirmation of the HSR pharmacokinetic profile are essential in evaluating observed versus expected drug concentrations. We present and compare two murine meropenem-vaborbactam HSR profiles, their potential impact on bacterial killing, and clinical translatability.

Keywords: human-simulated exposure; murine model; pharmacodynamics; pharmacokinetics; β-lactams.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / therapeutic use
  • Humans
  • Mice

Substances

  • Anti-Bacterial Agents