Efficacy of linezolid in a staphylococcal endocarditis rabbit model

A rabbit endocarditis model was used to test the efficacy of oral linezolid and iv vancomycin. Twenty-four hours after catheter placement across the a ortic valve, rabbits were infected with 3.5 x 10(6) cfu of Staphylococcus a ureus (UC-9258). Two days after infection, control rabbits were killed, and treated rabbits were given 5 days of therapy with linezolid at 8 h interva ls (tds) using either 25, 50 or 75 mg/kg/dose, or vancomycin at 12 h interv als (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 t he control. Linezolid at 25 mg/kg was ineffective. The efficacy of 75 and 5 0 mg/kg linezolid was related to maintenance of plasma drug levels near or above the linezolid MIC for UC-9258 (2 mg/L).