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Efficacy of Telavancin in the Treatment of Experimental Endocarditis Due to Glycopeptide-Intermediate Staphylococcus aureus

José M. Miró,^* Cristina García-de-la-Mària, Yolanda Armero, Elisa de-Lazzari, Dolors Soy, Asunción Moreno, Ana del Rio, Manel Almela, Carlos A. Mestres, José M. Gatell, María-Teresa Jiménez-de-Anta, Francesc Marco, and the Hospital Clínic Experimental Endocarditis Study Group

Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Received 10 October 2006/ Returned for modification 11 December 2006/ Accepted 23 April 2007

The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate Staphylococcus aureus: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 µg/ml and 6 µg/ml, respectively, for telavancin and 46 µg/ml and 6 µg/ml, respectively, for vancomycin. In glycopeptide-intermediate S. aureus ATCC 700788, telavancin sterilized 6 of 16 vegetations (37%), whereas vancomycin sterilized 4 of 20 (20%) (P = 0.29) compared with 0 of 17 in the control group. In HIP 5836 experiments, telavancin and vancomycin sterilized 5 of 16 (31%) and 1 of 15 (7%) vegetations (P = 0.17), respectively, compared with none in the control group. Telavancin reduced vegetation titers by 2.0 and 2.3 logs greater than vancomycin for the ATCC 700788 (4.6 [2.0 to 5.8] versus 6.6 [2.0 to 6.9] log CFU/g vegetation; P = 0.05) and HIP 5836 (4.4 [2.0 to 7.4] versus 6.7 [4.5 to 8.7] log CFU/g vegetation; P = 0.09) strains, respectively; these differences did not reach statistical significance. All isolates from vegetations remained susceptible to telavancin after therapy. The results suggest that telavancin may be an effective treatment for endocarditis caused by glycopeptide-intermediate S. aureus.

Published ahead of print on 7 May 2007.

Members of the Hospital Clínic Endocarditis Study Group of the Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain, include the following: Infectious Diseases Service, J. M. Miró, A. Moreno, A. del Rio, and J. M. Gatell; Microbiology Service, F. Marco, C. García de la Mària, Y. Armero, M. Almela, and M. T. Jiménez de Anta; Cardiovascular Institute, C. A. Mestres, R. Cartaña, S. Ninot, J. L. Pomar, M. Azqueta, M. Sitges, J. C. Paré, and G. Sanz; Pathology Department, N. Perez, J. Ramírez, and T. Ribalta; Toxicology Service, M. Brunet; Pharmacy Service, D. Soy; and Epidemiology and Statistics Unit, E. de Lazzari.

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