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JAC Advance Access published online on April 27, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki109
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received October 6, 2004
Revised January 13, 2005
Accepted March 1, 2005

Original article

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

Li-Yan Yin 1, Luca Lazzarini 2, Fan Li 3, C. Melinda Stevens 3, and Jason H. Calhoun 4*

1 Department of Orthopaedic Surgery, University of Missouri, Columbia, MO, USA
2 Infectious Diseases Unit, Department of Internal Medicine, San Bortolo Hospital, Vicenza, Italy
3 Department of Orthopedics and Rehabilitation, The University of Texas Medical Branch, Galveston, TX, USA
4 Department of Orthopaedic Surgery, University of Missouri, Columbia, MO, USA;

* To whom correspondence should be addressed.
Jason H. Calhoun, E-mail: calhounj{at}health.missouri.edu


  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 (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/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.

Keywords: MRSA; antibiotics; infections.
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