In vitro activity of fosfomycin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy

Infez Med. 2005 Jun;13(2):97-102.

Abstract

Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteremia / etiology
  • Bacteremia / microbiology*
  • Blood Vessel Prosthesis
  • Catheterization*
  • Device Removal
  • Drainage*
  • Drug Evaluation, Preclinical
  • Drug Resistance, Bacterial
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Electrophoresis, Gel, Pulsed-Field
  • Equipment Contamination
  • Fosfomycin / administration & dosage
  • Fosfomycin / pharmacology*
  • Glycopeptides / pharmacology
  • Humans
  • Mediastinitis / etiology
  • Mediastinitis / microbiology
  • Methicillin Resistance
  • Pacemaker, Artificial*
  • Postoperative Complications / microbiology
  • Prosthesis-Related Infections / microbiology*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / isolation & purification
  • Teicoplanin / administration & dosage
  • Teicoplanin / pharmacology*
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Glycopeptides
  • Fosfomycin
  • Teicoplanin
  • Vancomycin