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Title
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Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis
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Author
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Abstract
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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 log10 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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Language
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English
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Source (journal)
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American journal of respiratory and critical care medicine. - New York, 1994, currens
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Publication
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New York
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2009
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ISSN
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1073-449X
[print]
1535-4970
[online]
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DOI
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10.1164/RCCM.200807-1152OC
10.1164/RCCRN.200807-1152OC
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Volume/pages
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180
:6
(2009)
, p. 553-557
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ISI
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000270002600011
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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