Comparative evaluation of tigecycline and vancomycin with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model

Abstract

Objectives: Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. Methods: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14mg/kg twice daily), with and without oral rifampicin (40mg/kg twice daily); or subcutaneous administration of vancomycin (30mg/kg twice daily), with and without oral rifampicin (40mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 106 colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. Results: Rabbits that received tigecycline and oral rifampicin therapy (n = 14) showed a 100% infection clearance. Rabbits treated with tigecycline (n = 10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n = 10) also showed a 90% clearance. Rabbits treated with vancomycin (n = 11) showed an 81.8% clearance. Untreated controls (n = 15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. Conclusions: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.