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JAC Advance Access originally published online on August 1, 2007
Journal of Antimicrobial Chemotherapy 2007 60(4):819-823; doi:10.1093/jac/dkm271
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© The Author 2007. 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

Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections

Gary E. Stein1,*, Sharon Schooley1, Charles A. Peloquin2, Anne Missavage1 and Daniel H. Havlichek1

1 Michigan State University—School of Medicine, B320 Life Science Building, East Lansing, MI 48824, USA 2 National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA

Received 22 May 2007; returned 15 June 2007; revised 25 June 2007; accepted 26 June 2007


* Corresponding author. Tel: +1-517-353-5126; Fax: +1-517-353-1922; E-mail: steing{at}msu.edu

Objectives: Linezolid soft tissue penetration and serum antimicrobial activity were analysed in six patients with peripheral vascular disease and severe diabetic foot infections requiring surgical intervention.

Methods: Blood draws (1, 3, 6, 9 and 12 h after initiation of a 1 h infusion) and a viable soft tissue sample at the site of infection were obtained in patients receiving linezolid (600 mg every 12 h) on the day of surgery. Concentrations of linezolid were determined by HPLC in both tissue (pre-treated with tissue lysis buffer) and serum. In addition, serum inhibitory and bactericidal activity (dilution titres 1:2–1:32) of linezolid was determined in these patients against strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (vancomycin MICs = 2, 4, 8, 256 and >256 mg/L).

Results: Linezolid concentrations in tissue were found to be 51% (range, 18% to 78%) of simultaneous serum concentrations. Rapid (1 h) and prolonged (12 h) inhibitory activity (titres ≥ 1:2) was observed for linezolid against each of the study isolates. Furthermore, bactericidal activity (titres ≥ 1:2) was observed for at least 6 h (50% of the dosing interval) against four of these five strains.

Conclusions: These findings suggest that linezolid could be effective in the treatment of multidrug-resistant MRSA even when concentrations at the infection site are diminished due to impaired blood flow.

Keywords: pharmacokinetics , pharmacodynamics , diabetic foot infections


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