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
- 1 September 2007
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 51 (9), 3311-3316
- https://doi.org/10.1128/aac.01470-06
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× 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× MIC and 1× 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.Keywords
This publication has 23 references indexed in Scilit:
- Efficacy of Telavancin in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant Staphylococcus aureus or Vancomycin-Intermediate Staphylococcus aureusAntimicrobial Agents and Chemotherapy, 2005
- Telavancin: in vitro activity against staphylococci in a biofilm modelJournal of Antimicrobial Chemotherapy, 2005
- Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs: an updateJournal of Antimicrobial Chemotherapy, 2005
- Pharmacokinetics, Serum Inhibitory and Bactericidal Activity, and Safety of Telavancin in Healthy SubjectsAntimicrobial Agents and Chemotherapy, 2005
- Pharmacodynamic studies of amoxicillin against Streptococcus pneumoniae: comparison of a new pharmacokinetically enhanced formulation (2000 mg twice daily) with standard dosage regimensJournal of Antimicrobial Chemotherapy, 2004
- Pharmacodynamics of Telavancin (TD-6424), a Novel Bactericidal Agent, against Gram-Positive BacteriaAntimicrobial Agents and Chemotherapy, 2004
- Influence of protein binding under controlled conditions on the bactericidal activity of daptomycin in an in vitro pharmacodynamic modelJournal of Antimicrobial Chemotherapy, 2004
- In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium sppAntimicrobial Agents and Chemotherapy, 2004
- Pharmacokinetic and Pharmacodynamic Parameters for Antimicrobial Effects of Cefotaxime and Amoxicillin in an In Vitro Kinetic ModelAntimicrobial Agents and Chemotherapy, 2001
- Comparative in vitro pharmacodynamics of BO-2727, meropenem and imipenem against Gram-positive and Gram-negative bacteriaClinical Microbiology & Infection, 1997