title: Durable cure for tuberculosis: rifalazil in combination with isoniazid in a murine model of Mycobacterium tuberculosis infection.
abstract: 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.
authors.affiliation: State University of New York Upstate Medical University, Syracuse, NY, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Shoen
authors.forename: M S
authors.initials: MS
authors.lastname: DeStefano
authors.forename: M H
authors.initials: MH
authors.lastname: Cynamon
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D012294:Rifamycins / Q000627:therapeutic use*; D013154:Spleen / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D005938:Glucocorticoids; D012294:Rifamycins; C068980:KRM 1648; D003907:Dexamethasone; D007538:Isoniazid