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

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 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 g/ml and 6 g/ml, respectively, for telavancin and 46 g/ml and 6 g/ml, respectively, for vancomycin.

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus

“…(b) The mathematical models were applied to obtain the required infusion doses to simulate the human kinetics of FOF and IPM as an open one-compartment model (58) and to obtain the required infusion doses to simulate the human kinetics of CRO as an open two-compartment model (59). (c) Simulation of the human profiles was done in healthy rabbits as reported previously (60). The study of the human-like pharmacokinetics profile for VAN was already performed and was published previously (60).…”

“…(c) Simulation of the human profiles was done in healthy rabbits as reported previously (60). The study of the human-like pharmacokinetics profile for VAN was already performed and was published previously (60).…”

“…Experimental aortic valve IE was induced according to the method described by Garrison and Freedman (61). A catheter was inserted through the right carotid artery into the left ventricle, while antibiotics were administered into the inferior vena cava through a jugular vein catheter, as previously described (60).…”

“…The infected rabbits were randomized to receive intravenously no therapy (control); vancomycin at a standard dose (VAN-SD) (simulating 1 g q12h), vancomycin at a high dose (VAN-HD) (simulating 1 g q6h), FOF (simulating 2 g q6h), IPM (simu- (v) Analysis of endocardial vegetations. After antibiotic treatment, rabbits were killed and aortic valve vegetations were removed and processed as previously described (60). Only those animals with proper placement of the catheter, macroscopic evidence of vegetations at the time of death, and S. aureus in cultures of blood obtained before the start of antimicrobial therapy were included in the study.…”

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

“…In brief, its efficacy and superiority compared with vancomycin or daptomycin has been documented in murine models of bacteremia or pneumonia by MRSA [105,106], in murine subcutaneous infection models, in rabbit endocarditis caused by MRSA, VISA, or daptomycin non-susceptible staphylococci [107][108][109], as well as in rabbit meningitis caused by penicillin-resistant pneumococcus [110,111]. It was equivalent to vancomycin or linezolid in a model of rabbit osteomyelitis caused by MRSA [112].…”