Efficacy of linezolid plus rifampin in an experimental model of methicillin-susceptible Staphylococcus aureus endocarditis.
The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combination were similar to those in the respective linezolid-only treatment groups. At therapeutic levels of linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the linezolid dosing, it did not antagonize the efficacy of linezolid.
Dailey
Charlene F
CF
Pharmacology, Pfizer, Kalamazoo, Michigan 49001, USA.
Pagano
Paul J
PJ
Buchanan
Lewis V
LV
Paquette
Jennifer A
JA
Haas
Joseph V
JV
Gibson
John K
JK
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006351:Heart Valves / Q000382:microbiology; D007668:Kidney / Q000382:microbiology; D000069349:Linezolid; D008297:Male; D008712:Methicillin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000627:therapeutic use*; D010406:Penicillins / Q000494:pharmacology*; D011817:Rabbits; D012293:Rifampin / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D023303:Oxazolidinones; D010406:Penicillins; D000069349:Linezolid; D008712:Methicillin; D012293:Rifampin