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Antimicrob. Agents Chemother. doi:10.1128/AAC.01266-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

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

^* To whom correspondence should be addressed. Email: jmmiro{at}ub.edu.

	Abstract

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 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 hours postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and MBCs, respectively, were 1 mg/L and 4 mg/L for telavancin and 8 mg/L and 128 mg/L for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/L and 8 mg/L for telavancin and 8 mg/L and 128 mg/L 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 GISA 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 log greater than vancomycin for the ATCC (4.6 [2.0-5.8] vs 6.6 [2.0-6.9] log CFU/g veg; p=0.05) and HIP (4.4 [2.0-7.4] vs 6.7 [4.5-8.7] log CFU/g veg; 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.

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