Activity of fosfomycin alone or combined with cefoxitin in vitro and in vivo in a murine model of urinary tract infection due to Escherichia coli harbouring CTX-M-15-type extended-spectrum β-lactamase

Int J Antimicrob Agents. 2014 Apr;43(4):366-9. doi: 10.1016/j.ijantimicag.2013.12.001. Epub 2013 Dec 11.

Abstract

The efficacy of fosfomycin alone or combined with cefoxitin was investigated in vitro and in a murine model of urinary tract infection due to susceptible Escherichia coli CFT073-RR and its transconjugant CFT073-RR Tc (pblaCTX-M-15) harbouring a plasmid carrying the blaCTX-M-15 gene. In vitro, the combination of cefoxitin and fosfomycin was synergistic and bactericidal and prevented the emergence of fosfomycin-resistant mutants of CFT073-RR and CFT073-RR Tc (pblaCTX-M-15) that were selected with fosfomycin alone. In vivo, the combination conferred an advantage in terms of kidney sterilisation of mice infected with either strain compared with fosfomycin monotherapy.

Keywords: Cefoxitin; Escherichia coli; Extended-spectrum β-lactamase; Fosfomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Cefoxitin / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / drug therapy
  • Female
  • Fosfomycin / therapeutic use*
  • Mice
  • Mice, Inbred CBA
  • Microbial Sensitivity Tests
  • Urinary Tract Infections / drug therapy*
  • beta-Lactam Resistance / genetics
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Fosfomycin
  • Cefoxitin
  • beta-lactamase CTX-M-15
  • beta-Lactamases