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JAC Advance Access published online on August 5, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl311
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received April 24, 2006
Revised June 26, 2006
Accepted July 5, 2006

Original article

Pharmacodynamics of dalbavancin studied in an in vitro pharmacokinetic system

Karen E. Bowker 1, Alan R. Noel 1, and Alasdair P. MacGowan 1 *

1 Bristol Centre for Antimicrobial Research & Evaluation, North Bristol NHS Trust and University of Bristol, Bristol, UK

* To whom correspondence should be addressed.
Alasdair P. MacGowan, E-mail: alasdair.macgowan{at}nbt.nhs.uk


  Abstract

Objectives: The antibacterial effect of dalbavancin was studied against Staphylococcus aureus using stepwise declining concentrations designed to model a range of free drug concentrations observed in human serum.

Methods: Initial concentrations ranged from 0.6 to 21 mg/L and experiments were conducted over 240 h. Three vancomycin-susceptible and one vancomycin-intermediate strain of S. aureus were used.

Results and conclusions: Dalbavancin showed non-concentration-dependent killing against the three vancomycin-susceptible strains in the range 3-21 mg/L and the vancomycin-intermediate strain at 15 and 21 mg/L. AUC/MIC could be related to antibacterial effect. The AUC/MIC for a bacteriostatic effect was 36 at 24 h, 55 at 120 h and 100 at 240 h. A larger AUC/MIC was required to produce a 2 log reduction in counts, being 214 at 24 h, 195 at 120 h and 331 at 240 h.

Keywords: AUC/MIC; S. aureus; VISA.
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