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JAC Advance Access originally published online on April 28, 2008
Journal of Antimicrobial Chemotherapy 2008 62(2):381-383; doi:10.1093/jac/dkn180
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© The Author 2008. 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

Original research

Efficacy and pharmacodynamics of linezolid, alone and in combination with rifampicin, in an experimental model of methicillin-resistant Staphylococcus aureus endocarditis

Thomas Tsaganos*, Ioannis Skiadas, Pantelis Koutoukas, Theodoros Adamis, Nikos Baxevanos, Ira Tzepi, Aimilia Pelekanou, Evangelos J. Giamarellos-Bourboulis, Helen Giamarellou and Kyriaki Kanellakopoulou

4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece

Received 31 December 2007; returned 6 February 2008; revised 25 March 2008; accepted 31 March 2008

* Correspondence address. 4th Department of Internal Medicine, Attikon University Hospital, 1 Rimini Street, Athens 124 62, Greece. Tel: +30-210-58-31-985; Fax: +30-210-53-26-446; E-mail: tsag{at}freemail.gr

Objectives: To evaluate the efficacy of oral linezolid, with or without rifampicin, on valve vegetations and secondary foci of infection compared with vancomycin, in the absence or presence of rifampicin, in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.

Methods: Treatment groups were controls (n = 16), linezolid (n = 15), vancomycin (n = 15), linezolid and rifampicin (n = 15), vancomycin and rifampicin (n = 13), linezolid relapse (n = 11) and vancomycin relapse (n = 9). Therapy lasted 5 days in all groups, with survival of animals in the linezolid relapse and vancomycin relapse groups being recorded for an additional 5 days. Blood was drawn to determine the linezolid concentration, and valve vegetations, and kidney, liver, lung and spleen segments were collected for culture.

Results: Survival in each individual group was higher than that in the control group; bacterial load in valve vegetations was reduced by all treatment regimens, with linezolid exhibiting bactericidal effects. Bactericidal activity of linezolid was noted in all secondary foci of infection except the lung, where only the combination of rifampicin with linezolid was bactericidal.

Conclusions: Orally administered linezolid is effective in limiting bacterial growth in the secondary foci of endocarditis. Co-administration of rifampicin favoured the suppression of bacterial growth in the lung.

Keywords: vancomycin , pharmacokinetics , secondary foci , tissues


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