In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Multidrug-Resistant Pseudomonas aeruginosa in the Neutropenic Murine Thigh Infection Model

Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00233-19. doi: 10.1128/AAC.00233-19. Print 2019 Jul.

Abstract

We describe the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) exposure against multidrug-resistant Pseudomonas aeruginosa (meropenem MICs 8 to >256 μg/ml) in a neutropenic murine thigh infection model. WCK 5222 MICs ranged from 4 to 32 μg/ml. Substantial in vivo WCK 5222 activity was observed against all isolates, further enhancing the efficacy of zidebactam alone in 11/16 isolates (WCK 5222 mean reduction, -1.62 ± 0.58 log10 CFU/thigh), and a lack of activity was observed with cefepime monotherapy.

Keywords: human simulated; pharmacodynamics; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / therapeutic use*
  • Cefepime / therapeutic use
  • Cephalosporins / therapeutic use*
  • Cyclooctanes / therapeutic use*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Piperidines / therapeutic use
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / pathogenicity*
  • Thigh / microbiology

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Cephalosporins
  • Cyclooctanes
  • Piperidines
  • WCK 5222
  • zidebactam
  • Cefepime