| Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis. | |
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MedLine Citation:
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PMID: 19590024 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined. OBJECTIVES: To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB. METHODS: Swiss mice were intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model). MEASUREMENTS AND MAIN RESULTS: Quantitative lung and spleen colony-forming unit counts and bacteriological relapse rates 3 months after the end of therapy were compared for the following regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)-containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated mice were culture negative after 4 months of therapy. The relapse rate in the group treated with 4 months of JHRZ was similar to that of mice treated for 6 months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6 vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in mice on once-daily basis. CONCLUSIONS: Four months of treatment with some J-containing regimens was as effective as the 6-month standard regimen and more effective than 4 months of treatment with M-containing regimens. Supplementation of standard regimen (RHZ) with J or substitution of J for H may shorten the treatment duration needed to cure TB in patients. |
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Authors:
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Murad Ibrahim; Chantal Truffot-Pernot; Koen Andries; Vincent Jarlier; Nicolas Veziris |
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Publication Detail:
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Type: Journal Article Date: 2009-07-09 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 180 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-07 Completed Date: 2009-10-01 Revised Date: 2013-04-10 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 553-7 Citation Subset: AIM; IM |
Affiliation:
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Laboratoire de Bactériologie-Hygiène, Université Pierre et Marie Curie, Université Paris 6, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antitubercular Agents / pharmacology* Disease Models, Animal Drug Therapy, Combination Female Hydrolases / biosynthesis Isoniazid / pharmacology Mice Mycobacterium tuberculosis / growth & development, metabolism Pyrazinamide / pharmacology Quinolines / pharmacology* Rifampin / pharmacology Tuberculosis / drug therapy*, microbiology, pathology Tuberculosis, Pulmonary / drug therapy, microbiology, pathology Tuberculosis, Splenic / drug therapy, microbiology, pathology |
| Chemical | |
Reg. No./Substance:
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0/Antitubercular Agents; 0/Quinolines; 13292-46-1/Rifampin; 54-85-3/Isoniazid; 78846I289Y/Bedaquiline; 98-96-4/Pyrazinamide; EC 3.-/Hydrolases; EC 3.7.-/HsaD protein, Mycobacterium tuberculosis |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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