Skip Navigation


JAC Advance Access originally published online on October 24, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1177-1184; doi:10.1093/jac/dkl424
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
58/6/1177    most recent
dkl424v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Barcia-Macay, M.
Right arrow Articles by Van Bambeke, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barcia-Macay, M.
Right arrow Articles by Van Bambeke, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus

Maritza Barcia-Macay, Sandrine Lemaire, Marie-Paule Mingeot-Leclercq, Paul M. Tulkens and Françoise Van Bambeke*

Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain B-1200 Brussels, Belgium

Received 26 July 2006; returned 29 August 2006; revised 15 September 2006; accepted 25 September 2006

*Correspondence address. UCL 7370, Avenue E. Mounier 73, B-1200, Brussels, Belgium. Tel: +32-2-764-7378; Fax: +32-2-764-7373; E-mail: vanbambeke{at}facm.ucl.ac.be

Objectives: To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA).

Methods: Determination of cfu changes (3–24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000x MIC.

Results: Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration–effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3–1x MIC and 100–1000x MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [–3 log (MSSA) to –1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. –0.5 log decrease at 24 h and at Cmax).

Conclusions: Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.

Keywords: lipoglycopeptide , Gram-positive , bactericidal , phagolysosomes , concentration dependence


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
S. Lemaire, A. Olivier, F. Van Bambeke, P. M. Tulkens, P. C. Appelbaum, and Y. Glupczynski
Restoration of Susceptibility of Intracellular Methicillin-Resistant Staphylococcus aureus to {beta}-Lactams: Comparison of Strains, Cells, and Antibiotics
Antimicrob. Agents Chemother., August 1, 2008; 52(8): 2797 - 2805.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
M. Barcia-Macay, F. Mouaden, M.-P. Mingeot-Leclercq, P. M. Tulkens, and F. Van Bambeke
Cellular pharmacokinetics of telavancin, a novel lipoglycopeptide antibiotic, and analysis of lysosomal changes in cultured eukaryotic cells (J774 mouse macrophages and rat embryonic fibroblasts)
J. Antimicrob. Chemother., June 1, 2008; 61(6): 1288 - 1294.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Lemaire, C. Fuda, F. Van Bambeke, P. M. Tulkens, and S. Mobashery
Restoration of Susceptibility of Methicillin-resistant Staphylococcus aureus to {beta}-Lactam Antibiotics by Acidic pH: ROLE OF PENICILLIN-BINDING PROTEIN PBP 2a
J. Biol. Chem., May 9, 2008; 283(19): 12769 - 12776.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
R. J. Attwood and K. L. LaPlante
Telavancin: A novel lipoglycopeptide antimicrobial agent
Am. J. Health Syst. Pharm., November 15, 2007; 64(22): 2335 - 2348.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. Lemaire, F. Van Bambeke, M.-P. Mingeot-Leclercq, and P. M. Tulkens
Modulation of the Cellular Accumulation and Intracellular Activity of Daptomycin towards Phagocytized Staphylococcus aureus by the P-Glycoprotein (MDR1) Efflux Transporter in Human THP-1 Macrophages and Madin-Darby Canine Kidney Cells
Antimicrob. Agents Chemother., August 1, 2007; 51(8): 2748 - 2757.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.