Efficacy of telavancin in the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis: studies with a rabbit model.
OBJECTIVE
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.
Yin
Li-Yan
LY
Department of Orthopaedic Surgery, University of Missouri-Columbia, Columbia, MO 65212, USA.
Calhoun
Jason H
JH
Thomas
Theodore S
TS
Wirtz
Eric D
ED
D000081:Acetamides / Q000627:therapeutic use; D000617:Aminoglycosides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000382:microbiology; D015169:Colony Count, Microbial; D000069349:Linezolid; D000077427:Lipoglycopeptides; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D023303:Oxazolidinones / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
D000081:Acetamides; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid; C487637:telavancin