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Antimicrobial Agents and Chemotherapy, May 1999, p. 1189-1191, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activities of Several Novel Oxazolidinones against Mycobacterium tuberculosis in a Murine Model

M. H. Cynamon,* S. P. Klemens, C. A. Sharpe, and S. Chase

Veteran Affairs Medical Center and State University of New York Health Science Center, Syracuse, New York 13210

Received 20 October 1998/Returned for modification 29 December 1998/Accepted 25 February 1999

The activities of linezolid, eperezolid, and PNU-100480 were evaluated in a murine model of tuberculosis. Approximately 107 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.

* Corresponding author. Mailing address: Department of Medicine, Veteran Affairs Medical Center, 800 Irving Ave., Syracuse, NY 13210. Phone: (315) 476-7461, ext. 3324. Fax: (315) 476-5348. E-mail: Cynamon.Michael{at}Syracuse.VA.Gov.

Antimicrobial Agents and Chemotherapy, May 1999, p. 1189-1191, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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