In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 52, No. 1 ( 2008-01), p. 92-97
Abstract:
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 μg/ml at 8 h and 0.89 ± 1.03 μg/ml at 24 h) and extensively into AMs (19.0 ± 16.8 μg/ml at 8 h, 45.0 ± 22.4 μg/ml at 12 h, and 42.0 ± 31.4 μg/ml at 24 h). Mean concentrations in AMs and plasma at 12 h were 45.0 μg/ml and 22.9 μg/ml (mean AM/plasma ratio, 1.93), respectively, and at 24 h were 42.0 μg/ml and 7.28 μg/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 MIC 90 for methicillin-resistant Staphylococcus aureus (0.5 μg/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.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.00875-07
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2008
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
Permalink
