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JAC Advance Access originally published online on May 30, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):462-465; doi:10.1093/jac/dkl222
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Efficacy of telavancin in a murine model of bacteraemia induced by methicillin-resistant Staphylococcus aureus

Noe Reyes, Robert Skinner, Bret M. Benton, Kevin M. Krause, Josephine Shelton, Glenmar P. Obedencio and Sharath S. Hegde*

Theravance, Inc., 901 Gateway Boulevard, South San Francisco CA 94080, USA

Received 22 February 2006; returned 26 April 2006; revised 2 May 2006; accepted 4 May 2006

*Corresponding author. Tel: +1-650-808-6432; Fax: +1-650-808-6441; E-mail: shegde{at}theravance.com

Objectives: The efficacy of telavancin, a bactericidal lipoglycopeptide, was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in an immunocompromised murine model of bacteraemia.

Methods: Immunocompromised mice were inoculated intraperitoneally with S. aureus ATCC 33591 and treated with two subcutaneous doses (once every 12 h) of vehicle or test compound. Mouse pharmacokinetic data were generated and used to choose doses of telavancin (40 mg/kg) and vancomycin (110 mg/kg) in order to equate clinical exposures. Reduction in bacterial titre (in blood and spleen) and mortality were the two pharmacodynamic endpoints of the study.

Results: Mortality was 100% in animals treated with vehicle or vancomycin but was significantly lower (7%) in telavancin-treated animals. Telavancin produced significantly greater reductions in blood and spleen bacterial titres compared with vancomycin.

Conclusions: The data described here demonstrate that telavancin's in vivo bactericidal activity is superior to that of vancomycin against a single strain of MRSA and results in successful infection resolution and, consequently, improved survival in the murine bacteraemia model.

Keywords: lipoglycopeptides , MRSA , neutropenic , mice


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