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The pharmacodynamic effects of telavancin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the presence of human albumin or serum, and in an in vitro kinetic model.

Odenholt, Inga LU ; Lowdin, Elisabeth and Cars, Otto (2007) In Antimicrobial Agents and Chemotherapy 51(9). p.3311-3316
Abstract
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... (More)
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-log(10) 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 1 x MIC at 24 h. At all the other concentrations > 3-log(10) 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-log(10) killing was observed at 6 to 8 h. Unlike most antibiotics, telavancin was able to kill both strains in a nongrowing phase. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacodynamic telavancin methicillin-resistant methicillin-susceptible Staphylococcus aureus albumin vitro kinetic
in
Antimicrobial Agents and Chemotherapy
volume
51
issue
9
pages
3311 - 3316
publisher
American Society for Microbiology
external identifiers
  • wos:000249175400039
  • scopus:35948934631
ISSN
1098-6596
DOI
10.1128/AAC.01470-06
language
English
LU publication?
yes
id
f1404dab-2b55-4f5c-8f0c-fe8a45201873 (old id 540914)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17620377&dopt=Abstract
date added to LUP
2007-12-18 17:45:46
date last changed
2017-01-01 06:55:08
@article{f1404dab-2b55-4f5c-8f0c-fe8a45201873,
  abstract     = {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-log(10) 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 1 x MIC at 24 h. At all the other concentrations > 3-log(10) 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-log(10) killing was observed at 6 to 8 h. Unlike most antibiotics, telavancin was able to kill both strains in a nongrowing phase.},
  author       = {Odenholt, Inga and Lowdin, Elisabeth and Cars, Otto},
  issn         = {1098-6596},
  keyword      = {pharmacodynamic
telavancin
methicillin-resistant
methicillin-susceptible
Staphylococcus
aureus
albumin
vitro
kinetic},
  language     = {eng},
  number       = {9},
  pages        = {3311--3316},
  publisher    = {American Society for Microbiology},
  series       = {Antimicrobial Agents and Chemotherapy},
  title        = {The pharmacodynamic effects of telavancin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the presence of human albumin or serum, and in an in vitro kinetic model.},
  url          = {http://dx.doi.org/10.1128/AAC.01470-06},
  volume       = {51},
  year         = {2007},
}