Phenotypic/Genotypic Profile of OXA-10-Like-Harboring, Carbapenem-Resistant Pseudomonas aeruginosa: Using Validated Pharmacokinetic/Pharmacodynamic In Vivo Models To Further Evaluate Enzyme Functionality and Clinical Implications

Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0127421. doi: 10.1128/AAC.01274-21. Epub 2021 Jul 26.

Abstract

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of β-lactamase variants.

Keywords: Pseudomonas aeruginosa; carbapenem resistant; cefepime; ceftazidime; in vivo; pharmacodynamics; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenems / pharmacology
  • Ceftazidime / pharmacology
  • Cephalosporins / pharmacology
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Phenotype
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas aeruginosa* / genetics
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Cephalosporins
  • Ceftazidime
  • beta-lactamase PSE-2
  • beta-Lactamases