Efficacy of telavancin in the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis: studies with a rabbit model

J Antimicrob Chemother. 2009 Feb;63(2):357-60. doi: 10.1093/jac/dkn490. Epub 2008 Dec 5.

Abstract

Objectives: Staphylococcus aureus is the most common pathogen isolated in osteomyelitis. This study evaluated the efficacies of telavancin (an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action against Gram-positive bacteria), vancomycin and linezolid in a rabbit methicillin-resistant S. aureus (MRSA) osteomyelitis model.

Methods: Localized osteomyelitis was induced in New Zealand White rabbits by percutaneous injection of 10(6) cfu of MRSA clinical isolate 168-1 into the intramedullary cavity. Two weeks post-infection, rabbits with radiographically confirmed, localized proximal tibial osteomyelitis were randomized into four groups (n = 15 per group): untreated controls; vancomycin 30 mg/kg subcutaneously every 12 h; linezolid 60 mg/kg orally every 8 h; and telavancin 30 mg/kg subcutaneously every 12 h. After 4 weeks of antibiotic treatment, animals were left untreated for 2 weeks. Rabbits were then euthanized and the tibias harvested. Bone matrix and marrow from each tibia were cultured and bacterial counts determined.

Results: For MRSA isolate 168-1, the MIC was 0.25 mg/L for telavancin, 0.5 mg/L for vancomycin and 0.5 mg/L for linezolid. Tibial cultures were positive for MRSA in 9 of 15 (60%) untreated controls, and 3 of 15 (20%) telavancin-treated, 3 of 15 (20%) vancomycin-treated and 4 of 14 (29%) linezolid-treated rabbits.

Conclusions: Telavancin has comparable efficacy to vancomycin and linezolid in a rabbit model of MRSA osteomyelitis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / therapeutic use
  • Aminoglycosides / therapeutic use*
  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Bone Marrow / microbiology
  • Colony Count, Microbial
  • Linezolid
  • Lipoglycopeptides
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / microbiology
  • Oxazolidinones / therapeutic use
  • Rabbits
  • Random Allocation
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Treatment Outcome
  • Vancomycin / therapeutic use

Substances

  • Acetamides
  • Aminoglycosides
  • Anti-Bacterial Agents
  • Lipoglycopeptides
  • Oxazolidinones
  • Vancomycin
  • Linezolid
  • telavancin