Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosa Clinical Isolates and Isogenic β-Lactam-Resistant Mutants

Antimicrob Agents Chemother. 2020 Jan 27;64(2):e02165-19. doi: 10.1128/AAC.02165-19. Print 2020 Jan 27.

Abstract

Imipenem and imipenem-relebactam MICs were determined for 1,445 Pseudomonas aeruginosa clinical isolates and a large panel of isogenic mutants showing the most relevant mutation-driven β-lactam resistance mechanisms. Imipenem-relebactam showed the highest susceptibility rate (97.3%), followed by colistin and ceftolozane-tazobactam (both 94.6%). Imipenem-relebactam MICs remained ≤2 μg/ml in all 16 isogenic PAO1 mutants and in 8 pairs of extensively drug-resistant clinical strains that had developed resistance to ceftolozane-tazobactam and ceftazidime-avibactam due to mutations in OXA-10 or AmpC.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; extensively drug resistant; imipenem-relebactam; multidrug resistance; whole-genome sequencing; β-lactam resistance mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Colistin / pharmacology*
  • Humans
  • Imipenem / pharmacology*
  • Mutation
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / genetics
  • beta-Lactam Resistance
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Imipenem
  • beta-Lactamases
  • relebactam
  • Colistin