title: Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model.
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.
authors.affiliation: Veteran Affairs Medical Center and State University of New York Health Science Center, Syracuse, New York 13210, USA. Cynamon.Michael@Syracuse.VA.Gov
authors.forename: M H
authors.initials: MH
authors.lastname: Cynamon
authors.forename: S P
authors.initials: SP
authors.lastname: Klemens
authors.forename: C A
authors.initials: CA
authors.lastname: Sharpe
authors.forename: S
authors.initials: S
authors.lastname: Chase
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000069349:Linezolid; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D023303:Oxazolidinones; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D010080:Oxazoles; D023303:Oxazolidinones; C098012:U 100480; C098011:eperezolid; D000069349:Linezolid