Prophylactic efficacy of linezolid alone or combined with levofloxacin and vancomycin in a rat subcutaneous pouch model of graft infection caused by Staphylococcus epidermidis with intermediate resistance to glycopeptides

J Antimicrob Chemother. 2003 Oct;52(4):724-6. doi: 10.1093/jac/dkg396. Epub 2003 Sep 1.

Abstract

Objectives: A rat model was used to investigate the efficacy of linezolid, alone or in combination with levofloxacin and vancomycin, in the prevention of vascular prosthetic graft infection resulting from methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides.

Methods: Graft infections were established in the subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses, followed by topical inoculation with S. epidermidis. The study comprised: one group without inoculation; one inoculated group without prophylaxis; six inoculated groups that received intraperitoneal linezolid (8 mg/kg), levofloxacin (7 mg/kg) or vancomycin (7 mg/kg) alone or in combination at the dosages mentioned above. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture.

Results: Quantitative graft cultures from animals treated with a single drug showed a significant efficacy only for linezolid. The efficacy of levofloxacin was similar to that of vancomycin. Combination studies demonstrated that only the treatments that included linezolid produced no evidence of staphylococcal infection.

Conclusions: Linezolid as perioperative prophylaxis can be useful for the prevention of graft infections caused by multiresistant staphylococcal strains.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / pharmacology
  • Acetamides / therapeutic use
  • Animals
  • Antibiotic Prophylaxis / methods*
  • Drug Resistance, Bacterial* / drug effects
  • Drug Resistance, Bacterial* / physiology
  • Drug Therapy, Combination / pharmacology
  • Drug Therapy, Combination / therapeutic use*
  • Glycopeptides / pharmacology
  • Glycopeptides / therapeutic use*
  • Graft Rejection / drug therapy*
  • Graft Rejection / microbiology
  • Levofloxacin
  • Linezolid
  • Male
  • Microbial Sensitivity Tests
  • Ofloxacin / pharmacology
  • Ofloxacin / therapeutic use
  • Oxazolidinones / pharmacology
  • Oxazolidinones / therapeutic use
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus epidermidis / drug effects*
  • Staphylococcus epidermidis / growth & development
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use

Substances

  • Acetamides
  • Glycopeptides
  • Oxazolidinones
  • Levofloxacin
  • Vancomycin
  • Ofloxacin
  • Linezolid