In vitro activity of cefepime/zidebactam (WCK 5222) against recent Gram-negative isolates collected from high resistance settings of Greek hospitals

Diagn Microbiol Infect Dis. 2021 Jul;100(3):115327. doi: 10.1016/j.diagmicrobio.2021.115327. Epub 2021 Jan 30.

Abstract

Cefepime/zidebactam is in clinical development for the treatment of carbapenem-resistant Gram-negative infections. MICs of cefepime/zidebactam (1:1) and comparators against Enterobacterales (n = 563), Pseudomonas (n = 172) and Acinetobacter baumannii (n =181) collected from 15 Greek hospitals (2014-2018) were determined by reference broth microdilution method. The isolates exhibited high carbapenem resistance rates [(Enterobacterales (75%), Pseudomonas (75%) and A. baumannii (98.3%)]. Cefepime/zidebactam showed MIC50/90 of 0.5/2 mg/L, against Enterobacterales including metallo-β-lactamases (MBL)-producers. Reduced susceptibility rates to tigecycline (16.8%), colistin (47.4%), ceftazidime/avibactam (59.8%), and imipenem/relebactam (61%) indicated high prevalence of multi-drug resistance among Greek Enterobacterales. Cefepime/zidebactam exhibited MIC50/90 of 8/16 mg/L against Pseudomonas including MBL-producers. The MIC50/90 of ceftazidime/avibactam and imipenem/relebactam were high (≥32 mg/L). Cefepime/zidebactam showed MIC90 of 64 mg/L against A. baumannii which is within its therapeutic scope. Other antibiotics including colistin showed limited activity against A. baumannii. The activity of cefepime/zidebactam against multi-drug-resistant isolates is attributable to zidebactam mediated novel β-lactam-enhancer mechanism.

Keywords: Cefepime; Gram-negative bacteria; Greece; Multi-drug resistance; Zidebactam.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / pharmacology*
  • Cefepime / administration & dosage
  • Cefepime / pharmacology*
  • Cephalosporins / pharmacology*
  • Cyclooctanes / administration & dosage
  • Cyclooctanes / pharmacology*
  • Drug Resistance, Multiple, Bacterial*
  • Gram-Negative Bacteria / drug effects*
  • Greece
  • Hospitals
  • Humans
  • Microbial Sensitivity Tests
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*

Substances

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