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JAC Advance Access published online on April 6, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki106
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received October 21, 2004
Revised February 12, 2005
Accepted February 25, 2005

Brief report

Antibacterial activity of linezolid and vancomycin in an in vitro pharmacodynamic model of Gram-positive catheter-related bacteraemia

Nathan P. Wiederhold 1, Elizabeth A. Coyle 1, Issam I. Raad 2, Randall A. Prince 1, and Russell E. Lewis 3*

1 The University of Houston College of Pharmacy, Houston, TX, USA, USA; The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
2 The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
3 The University of Houston College of Pharmacy, Houston, TX, USA, USA; The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

* To whom correspondence should be addressed.
Russell E. Lewis, E-mail: rlewis{at}uh.edu


  Abstract

Objectives: The aim of this study was to compare the activity of linezolid and vancomycin in an in vitro pharmacodynamic model to assess potential differences in activity against biofilm-embedded organisms.

Methods: Single-lumen central venous catheters colonized with biofilm-embedded Staphylococcus aureus, Staphylococcus epidermidis or vancomycin-resistant Enterococcus faecium (VRE) were treated with simulated clinical dosing regimens of linezolid 600 mg every 12 h or vancomycin 1 g every 12 h in a one-compartment in vitro pharmacodynamic model. Quantitative cultures were sampled through the catheter and peripheral ports over 48 h to dynamically assess changes in the burden of catheter colonization and organism seeding, respectively. At 24 and 48 h catheters were removed, sonicated and cultured for adherent organisms.

Results: Both linezolid and vancomycin suppressed bacterial growth on the catheter and release of S. aureus and S. epidermidis into the model compared with controls (P < 0.05), while linezolid also suppressed counts compared with control and vancomycin versus VRE. Neither agent completely eradicated bacterial colonization of the catheters. MICs for the isolates recovered from the model did not increase over time with linezolid or vancomycin exposure.

Conclusions: Lack of activity against biofilm-embedded organisms appeared to be the primary reason for microbiological failure of both drugs in the model.

Keywords: Staphylococcus aureus; Enterococcus; biofilms.
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