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Antimicrobial Agents and Chemotherapy, August 2005, p. 3163-3165, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3163-3165.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficacy of Telavancin in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant Staphylococcus aureus or Vancomycin-Intermediate Staphylococcus aureus

Andres G. Madrigal, Li Basuino, and Henry F. Chambers*

Division of Infectious Diseases, San Francisco General Hospital, Department of Medicine, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, California 94110

Received 21 December 2004/ Returned for modification 11 February 2005/ Accepted 12 April 2005

The activities of telavancin and vancomycin were compared in vitro and in the rabbit model of aortic valve endocarditis against a methicillin-resistant Staphylococcus aureus strain, COL, and a vancomycin-intermediate S. aureus (VISA) strain, HIP 5836. Telavancin was bactericidal in time-kill studies at a concentration of 5 µg/ml against both COL and HIP5836. Vancomycin was bacteriostatic at 5 µg/ml and bactericidal at 10 µg/ml against COL and was bacteriostatic at 10 µg/ml against VISA strain HIP 5836. Compared to untreated controls, a twice-daily regimen of 30 mg/kg of telavancin reduced mean aortic valve vegetation titers of the COL strain by 4.7 log10 CFU/g after 4 days of therapy and sterilized 6/11 vegetations compared to 3.4 log10 CFU/g with 3/10 vegetations sterilized for a regimen of twice-daily vancomycin, 30 mg/kg; these differences were not statistically significant. Telavancin was significantly more effective than vancomycin in the VISA model, producing a 5.5 log10 CFU/g reduction versus no reduction in CFU with vancomycin. In experiments comparing 2-day regimens of telavancin at 30 mg/kg and 50 mg/kg twice daily, organisms were rapidly eliminated from vegetations, but the effect was not different between the two doses. These results suggest that telavancin may be an effective treatment for endocarditis and other serious staphylococcal infections accompanied by bacteremia, including infections caused by staphylococci not susceptible to vancomycin.

* Corresponding author. Mailing address: University of California at San Francisco, Division of Infectious Diseases at SFGH, Box 0811, San Francisco, CA 94143. Phone: (415) 206-5437. Fax: (415) 648-8425. E-mail: chipc{at}itsa.ucsf.edu.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3163-3165, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3163-3165.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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