Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 52, Issue 1, Pages 92-97Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00875-07
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Steady-state concentrations of telavancin, a novel, bactericidal lipoglycopeptide, were determined in the plasma, pulmonary epithelial lining fluid (ELF), and alveolar macrophages (AMs) of 20 healthy subjects. Telavancin at 10 mg of drug/kg of body weight/day was administered as a 1-h intravenous infusion on three successive days, with bronchoalveolar lavage performed on five subjects, each at 4, 8, 12, and 24 h after the last dose. Plasma samples were collected before the first and third infusions and at 1, 2, 3, 4, 8, 12, and 24 h after the third infusion. The plasma telavancin concentration-time profile was as reported previously. Telavancin (mean standard deviation) penetrated well into ELF(3.73 +/- 1.28 mu g/ml at 8 h and 0.89 +/- 1.03 mu g/ml at 24 h) and extensively into AMs (19.0 +/- 16.8 mu g/ml at 8 h, 45.0 +/- 22.4 mu g/ml at 12 h, and 42.0 +/- 31.4 mu g/ml at 24 h). Mean concentrations in AMs and plasma at 12 h were 45.0 mu g/ml and 22.9 mu g/ml (mean AM/plasma ratio, 1.93), respectively, and at 24 h were 42.0 mu g/ml and 7.28 mu g/ml (mean AM/plasma ratio, 6.67), respectively. Over the entire dosing interval, telavancin was present in ELF and AMs at concentrations up to 8-fold and 85-fold, respectively, above its MIC90 for methicillin-resistant Staphylococcus aureus (0.5 mu g/ml). Pulmonary surfactant did not affect telavancin's in vitro antibacterial activity. Telavancin was well tolerated. These results support the proposal for further clinical evaluation of telavancin for treating gram-positive respiratory infections.
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