Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model

The activities of linezolid, eperezolid, and PNU-100480 were evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old outbred CD-1 mice. In the first study, treatment was started 1 day postinfection and was given by gavage for 4 weeks. Viable cell counts were determined from homogenates of spleens and lungs. PNU-100180 was as active as isoniazid, Linezolid was somewhat less active than PNU-100480 and isoniazid, Eperezolid had little activity in this model. In the next two studies, treatment was started 1 week postinfection, A dose-response study was performed with PNU-100480 and linezolid (both at 25, 50, and 100 mg/kg of body weight). PNU-100480 was more active than linezolid, and its efficacy increased,vith an escalation of the dose. Subsequently, the activity of PNU-100480 alone and in combination,vith rifampin or isoniazid was evaluated and was compared to that of isoniazid-rifampin. The activity of PNU-100480 was similar to that of isoniazid and/or rifampin in the various combinations tested, Further evaluation of these oxazolidinones in the murine test system would be useful prior to the development of clinical studies with humans.