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JAC Advance Access originally published online on August 5, 2006
Journal of Antimicrobial Chemotherapy 2006 58(4):802-805; 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

Pharmacodynamics of dalbavancin studied in an in vitro pharmacokinetic system

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

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

Received 24 April 2006; returned 18 May 2006; revised 26 June 2006; accepted 5 July 2006

*Correspondence address. Bristol Centre for Antimicrobial Research & Evaluation, North Bristol NHS Trust, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK. Tel: +44-117-959-5651/2; Fax: +44-117-959-3154; E-mail: alasdair.macgowan{at}nbt.nhs.uk

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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