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Journal of Antimicrobial Chemotherapy (2001) 47, 349-352
© 2001 The British Society for Antimicrobial Chemotherapy

Brief report

Efficacy of linezolid in a staphylococcal endocarditis rabbit model

Martha P. Oramas-Shirey, Lewis V. Buchanan*, Christine L. Dileto-Fang, Charlene F. Dailey, Charles W. Ford, Donald H. Batts and John K. Gibson

Pharmacology 7250-209-205, 301 Henrietta Street, Pharmacia Corporation, Kalamazoo, MI 49001, USA

A rabbit endocarditis model was used to test the efficacy of oral linezolid and iv vancomycin. Twenty-four hours after catheter placement across the aortic valve, rabbits were infected with 3.5 x 106 cfu of Staphylococcus aureus (UC-9258). Two days after infection, control rabbits were killed, and treated rabbits were given 5 days of therapy with linezolid at 8 h intervals (tds) using either 25, 50 or 75 mg/kg/dose, or vancomycin at 12 h intervals (bd) using 25 mg/kg/dose. Linezolid at 75 and 50 mg/kg, and vancomycin significantly reduced S. aureus in aortic valve vegetations compared with the control. Linezolid at 25 mg/kg was ineffective. The efficacy of 75 and 50 mg/kg linezolid was related to maintenance of plasma drug levels near or above the linezolid MIC for UC-9258 (2 mg/L).

* Corresponding author. Tel: +1-616-833-4467; Fax: +1-616-833-9763; E-mail: lvbuchan{at}am.pnu.com


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