Transcending the challenge of evolving resistance mechanisms in Pseudomonas aeruginosa through β-lactam-enhancer-mechanism-based cefepime/zidebactam

mBio. 2023 Dec 19;14(6):e0111823. doi: 10.1128/mbio.01118-23. Epub 2023 Oct 27.

Abstract

Compared to other genera of Gram-negative pathogens, Pseudomonas is adept in acquiring complex non-enzymatic and enzymatic resistance mechanisms thus remaining a challenge to even novel antibiotics including recently developed β-lactam and β-lactamase inhibitor combinations. This study shows that the novel β-lactam enhancer approach enables cefepime/zidebactam to overcome both non-enzymatic and enzymatic resistance mechanisms associated with a challenging panel of P. aeruginosa. This study highlights that the β-lactam enhancer mechanism is a promising alternative to the conventional β-lactam/β-lactamase inhibitor approach in combating ever-evolving MDR P. aeruginosa.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; cefepime; zidebactam; ß-lactam enhancer; ß-lactamase inhibitor; ß-lactamases.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Azabicyclo Compounds* / pharmacology
  • Cefepime / pharmacology
  • Cephalosporins* / pharmacology
  • Cyclooctanes* / pharmacology
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests*
  • Piperidines
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa* / drug effects
  • Pseudomonas aeruginosa* / genetics
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Cyclooctanes
  • Cephalosporins
  • beta-Lactamase Inhibitors
  • Cefepime
  • cefepime-zidebactam
  • beta-Lactams
  • beta-Lactamases
  • zidebactam
  • Drug Combinations
  • Piperidines