Document Detail


Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis.
MedLine Citation:
PMID:  19590024     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Murad Ibrahim; Chantal Truffot-Pernot; Koen Andries; Vincent Jarlier; Nicolas Veziris
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Publication Detail:
Type:  Journal Article     Date:  2009-07-09
Journal Detail:
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:
Created Date:  2009-09-07     Completed Date:  2009-10-01     Revised Date:  2013-04-10    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-7     Citation Subset:  AIM; IM    
Affiliation:
Laboratoire de Bactériologie-Hygiène, Université Pierre et Marie Curie, Université Paris 6, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
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:
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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