Short-course treatment regimen to identify potential antituberculous agents in a murine model of tuberculosis.

Author(s): Shoen CM, DeStefano MS, Sklaney MR, Monica BJ, Slee AM, Cynamon MH

Affiliation(s): Central New York Research Corporation, Syracuse, NY 13210, USA.

Publication date & source: 2004-04, J Antimicrob Chemother., 53(4):641-5. Epub 2004 Feb 18.

Publication type: Clinical Trial; Randomized Controlled Trial

OBJECTIVE: Designing a more rapid method to test antimycobacterial agents in a murine model would significantly improve the drug development process. We describe a short-course in vivo treatment model that could be used to screen potential antituberculous drugs. METHODS: In this model, C57BL/6 mice were infected intranasally with approximately 10(6) viable Mycobacterium tuberculosis organisms. Treatment began 1 day post-infection and was administered for 2 days. Mice were euthanized 3 days post-infection and their right lungs were removed and cell counts determined. Several antimycobacterial agents with superior in vivo activity in a 4 week treatment model were tested to evaluate the short-course treatment model. RESULTS: Two days of isoniazid (25 mg/kg), rifampicin (20 mg/kg), PNU-100480 (100 mg/kg), gatifloxacin (100 mg/kg), levofloxacin (100 mg/kg) and sparfloxacin (100 mg/kg) were all able to significantly reduce the mycobacterial load in the lungs compared with the untreated control mice. CONCLUSIONS: Use of this model to screen potential chemotherapeutic agents will save time and resources.