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 aortic valve, rabbits were infected with 3.5 x 10(6) 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).
Pharmacology 7250-209-205, 301 Henrietta Street, Pharmacia Corporation, Kalamazoo, MI 49001, USA.
M P
MP
Oramas-Shirey
L V
LV
Buchanan
C L
CL
Dileto-Fang
C F
CF
Dailey
C W
CW
Ford
D H
DH
Batts
J K
JK
Gibson
D000081:Acetamides / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D007275:Injections, Intravenous; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000627:therapeutic use*; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid