Efficacy of telavancin in the treatment of experimental endocarditis due to glycopeptide-intermediate Staphylococcus aureus.
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.
Miró
José M
JM
Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. jmmiro@ub.edu
García-de-la-Mària
Cristina
C
Armero
Yolanda
Y
de-Lazzari
Elisa
E
Soy
Dolors
D
Moreno
Asunción
A
del Rio
Ana
A
Almela
Manel
M
Mestres
Carlos A
CA
Gatell
José M
JM
Jiménez-de-Anta
María-Teresa
MT
Marco
Francesc
F
D000617:Aminoglycosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001021:Aortic Valve / Q000382:microbiology; D015169:Colony Count, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000617:Aminoglycosides; D000890:Anti-Infective Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin