In vitro efficacy of fosfomycin-based combinations against clinical vancomycin-resistant Enterococcus isolates

Diagn Microbiol Infect Dis. 2013 Nov;77(3):254-7. doi: 10.1016/j.diagmicrobio.2013.07.012. Epub 2013 Sep 9.

Abstract

Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial pathogens, commonly causing catheter-related urinary tract infections or vascular catheter-related bloodstream infections. In this study, 10 Enterococcus faecium and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome-type VR clinical isolates were detected. The potential role of fosfomycin-based combination regimens for biofilm-related VRE infection is in vitro evaluated. Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline, rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based combinations were studied by time-kill method and a biofilm model. Of the fosfomycin-based combinations, a synergistic effect was particularly noted for teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin-based combinations, excluding rifampicin (40%), failed to enhance antibacterial activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%), or teicoplanin (44%). However, an antagonistic effect was found for ampicillin plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial activities of the drugs tested against VRE in vitro varied by species. Ampicillin exhibited potential activity against planktonic- and biofilm-embedded VR E. faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects against VRE even in the biofilm model, and this observation warrants further clinical studies.

Keywords: Biofilm; Synergistic effect; Vancomycin-resistant enterococci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Synergism
  • Enterococcus faecalis / drug effects*
  • Enterococcus faecalis / isolation & purification
  • Enterococcus faecium / drug effects*
  • Enterococcus faecium / isolation & purification
  • Fosfomycin / pharmacology*
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Vancomycin Resistance*

Substances

  • Anti-Bacterial Agents
  • Fosfomycin