A Once-Weekly R207910-containing Regimen Exceeds Activity of the Standard Daily Regimen in Murine Tuberculosis

dc.contributor.author Veziris, Nicolas
dc.contributor.author Ibrahim, Murad
dc.contributor.author Lounis, Nacer
dc.contributor.author Chauffour, Aurelie
dc.contributor.author Truffot-Pernot, Chantal
dc.contributor.author Andries, Koen
dc.contributor.author Jarlier, Vincent
dc.date.accessioned 2018-09-17T09:24:37Z
dc.date.available 2018-09-17T09:24:37Z
dc.date.issued 2008-11-23
dc.description.abstract Rationale: R207910 (TMC207 or J) is a member of the diarylquinolines, a new family of antituberculous drugs with high bactericidal activity when given daily in the murine model of tuberculosis. R207910 exhibits a long half-life and thus is a good candidate for once-weekly therapy of tuberculosis. Objectives: To study the activity of once-weekly R207910 monotherapy and combinations of R207910 with other antituberculous agents (isoniazid, rifapentine, moxifloxacin, and pyrazinamide). Methods: The established infection model of murine tuberculosis was used. Colony counts were determined in the lungs. Measurements and Main Results: Eight weeksofmonotherapy reduced the bacillary load by 3 to 4 log10 for rifapentine and by 5 to 6 log10 for R207910 (P , 0.05). The addition of rifapentine and isoniazid or moxifloxacin did not improve the bactericidal activity of R207910 monotherapy. In contrast, the triple combination of R207910 plus rifapentine plus pyrazinamide given once weekly for 2 months (i.e., a total of only eight administrations), was significantly (P , 0.05) more active than R207910 monotherapy or other R207910 combinations, and led to lung culture negativity in 9 of 10 mice, whereas all lungs were culture positive in the groups treated with other drug combinations. Moreover, R207910 plus rifapentine plus pyrazinamide given once weekly was more active than the current standard regimen of rifampin plus isoniazid plus pyrazinamide given five times per week. Conclusions: The unprecedented activity of the triple combination of R207910 plus rifapentine plus pyrazinamide suggests that it may be feasible to develop a fully intermittent once-weekly regimen. en_US
dc.identifier.issn 1073-449X
dc.identifier.uri https://dspace.alquds.edu/handle/20.500.12213/928
dc.language.iso en_US en_US
dc.publisher The American Thoracic Society en_US
dc.subject tuberculosis en_US
dc.subject animal models en_US
dc.subject directly observed therapy en_US
dc.subject R207910 en_US
dc.subject diarylquinolines en_US
dc.title A Once-Weekly R207910-containing Regimen Exceeds Activity of the Standard Daily Regimen in Murine Tuberculosis en_US
dc.type Article en_US
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