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

• Published in: Journal of antimicrobial chemotherapy 2004-04, Vol.53 (4), p.641-645
• Main Authors: Shoen, Carolyn M., DeStefano, Michelle S., Sklaney, Mary R., Monica, Bobbi J., Slee, Andrew M., Cynamon, Michael H.
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; animal models; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - administration & dosage; Biological and medical sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Female; Fluoroquinolones - administration & dosage; infectious diseases; Isoniazid - administration & dosage; Linezolid; Medical sciences; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Oxazolidinones - administration & dosage; Pharmacology. Drug treatments; Rifampin - administration & dosage; therapy; Time Factors; Tuberculosis - drug therapy; Tuberculosis - microbiology
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkh124

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.