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Pharmacodynamic effects of telavancin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains in the presence of human albumin or serum and in an in vitro kinetic model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
2007 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 51, no 9, 3311-3316 p.Article in journal (Refereed) Published
Abstract [en]

Telavancin is a novel bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens. The aim of this study was to describe the dynamics of the antimicrobial effect of telavancin against two strains of Staphylococcus aureus (methicillin susceptible and methicillin resistant) in an in vitro kinetic model with simulated human pharmacokinetics. Also, static experiments were performed to determine the rate and extent of killing by telavancin in the presence and absence of human albumin and human serum. Experiments in broth and in nutrient-depleted medium were performed to study the rate and extent of killing by telavancin of bacteria in different growth phases. In the in vitro kinetic model regrowth was noted at 24 h for both strains when exposed to initial concentrations below 5 mg/liter. There was a >3-log10 killing at all concentrations from 0.5 x MIC and above at 24 h both in broth and in the presence of 40-g/liter human albumin. In contrast to the methicillin-susceptible strain, the methicillin-resistant strain in 40-g/liter human albumin showed a regrowth at concentrations of 0.5 x MIC and 1x MIC at 24 h. At all the other concentrations >3-log10 killing was seen at 24 h. Concordant results were seen in 50% human serum. At a target area under the curve/MIC ratio of 50 (corresponding to the human dose of 10 mg/kg of body weight, administered intravenously), >3-log10 killing was observed at 6 to 8 h. Unlike most antibiotics, telavancin was able to kill both strains in a nongrowing phase.

Place, publisher, year, edition, pages
2007. Vol. 51, no 9, 3311-3316 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-14165DOI: 10.1128/AAC.01470-06ISI: 000249175400039PubMedID: 17620377OAI: oai:DiVA.org:uu-14165DiVA: diva2:41935
Available from: 2008-01-29 Created: 2008-01-29 Last updated: 2017-12-11Bibliographically approved

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Odenholt, IngaLöwdin, ElisabethCars, Otto

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