Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model.
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| Abstract |
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-100480 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 with an escalation of the dose. Subsequently, the activity of PNU-100480 alone and in combination with 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.
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| Authors | M H Cynamon, S P Klemens, C A Sharpe, S Chase |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 43 Issue 5 Pg. 1189-91 (May 1999) ISSN: 0066-4804 [Print] United States |
| PMID | 10223934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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