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

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.

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.

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.

Use of this model to screen potential chemotherapeutic agents will save time and resources.