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 microg/ml and 6 microg/ml, respectively, for
telavancin and 46 microg/ml and 6 microg/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.