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JAC Advance Access published online on February 18, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh124
© 2004 by The British Society for Antimicrobial Chemotherapy
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© 2004 The British Society for Antimicrobial Chemotherapy

Original article

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

Carolyn M. Shoen 1 , Michelle S. DeStefano 1 , Mary R. Sklaney 1 , Bobbi J. Monica 1 , Andrew M. Slee 2 , and Michael H. Cynamon 3 *

1 Central New York Research Corporation, Syracuse, NY;
2 Antimicrobial Research Department, DuPont Pharmaceuticals Company, Wilmington, DE;
3 Central New York Research Corporation, Syracuse, NY; Department of Medicine, Veterans Affairs Medical Center, Syracuse, NY, USA

* Corresponding author. E-mail: michael.cynamon{at}med.va.gov.

Received 29 August 2003 ; revised 26 November 2003 ; accepted 10 December 2003

Abstract

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 ~106 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.

Keywords: animal models, infectious diseases, Mycobacterium tuberculosis, therapy
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