Evaluation of the in vitro interaction of fosfomycin and meropenem against metallo-β-lactamase-producing Pseudomonas aeruginosa using Etest and time-kill assay

J Investig Med. 2021 Feb;69(2):371-376. doi: 10.1136/jim-2020-001573. Epub 2020 Oct 29.

Abstract

Pseudomonas aeruginosa is a nosocomial pathogen containing various resistance mechanisms. Among them, metallo-β-lactamase (MBL)-producing Pseudomonas are difficult to treat. Fosfomycin is an older antibiotic that has recently seen increased usage due to its activity against a broad spectrum of multidrug-resistant organisms. Our aim was to evaluate the combination of fosfomycin and meropenem against 20 MBL-producing P. aeruginosa (100% meropenem-resistant and 20% fosfomycin-resistant) using both an Etest minimal inhibitory concentration (MIC): MIC method and time-kill assay. MICs for fosfomycin and meropenem were determined by Etest and by broth microdilution method for the latter. The combination demonstrated synergy by Etest in 3/20 (15%) isolates and 5/20 (25%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 14/20 (70%) of isolates. No antagonism was found. Comparing both methods, Etest MIC: MIC method may be useful to rapidly evaluate other antimicrobial combinations.

Keywords: anti-bacterial agents; bacterial infections.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Disk Diffusion Antimicrobial Tests
  • Fosfomycin* / pharmacology
  • Meropenem* / pharmacology
  • Pseudomonas aeruginosa / drug effects*
  • beta-Lactamases

Substances

  • Anti-Bacterial Agents
  • Fosfomycin
  • beta-Lactamases
  • Meropenem