Journal Article

Durable Cure for Tuberculosis: Rifalazil in Combination with Isoniazid in a Murine Model of <i>Mycobacterium tuberculosis</i> Infection

Carolyn M. Shoen, Michelle S. DeStefano and Michael H. Cynamon

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 30, issue Supplement_3, pages S288-S290
Published in print June 2000 | ISSN: 1058-4838
Published online June 2000 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/313876
Durable Cure for Tuberculosis: Rifalazil in Combination with Isoniazid in a Murine Model of Mycobacterium tuberculosis Infection

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Rifalazil (formerly known as KRM-1648) in combination with isoniazid has been found to be more active than rifampin/isoniazid. Administration of rifalazil/isoniazid for 12 weeks resulted in continued apparent sterilization of organs 6 months after cessation of therapy. In this study we evaluated the durability of rifalazil/isoniazid treatment. Female CD-1 mice were infected with Mycobacterium tuberculosis ATCC 35801 (strain Erdman). Rifalazil and isoniazid were given in combination for 6 and 12 weeks; no mycobacteria could be cultured from spleens and lungs at both the 6-week and 12-week time points. After completing treatment, groups of mice treated with rifalazil/isoniazid for 6 or 12 weeks were observed without any additional treatment. These observation groups were compared to groups of rifalazil/isoniazid-treated mice (6 and 12 weeks) given dexamethasone for 7 and 8 weeks, respectively. Modest regrowth was noted in the spleens and lungs of the group treated with rifalazil/isoniazid for 6 weeks. Regrowth in the 6-weeks group was enhanced slightly by treatment with dexamethasone. In contrast, no regrowth was noted in the 12-weeks rifalazil/isoniazid group, and treatment with dexamethasone did not result in any regrowth.

Journal Article.  2213 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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