Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model.

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. Research Abstract Details 

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Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. Abstract Text:

Ian M Rosenthal,Ming Zhang,Kathy N Williams,Charles A Peloquin,Sandeep Tyagi,Andrew A Vernon,William R Bishai,Richard E Chaisson,Jacques H Grosset,Eric L Nuermberger,Ian M Rosenthal,Ming Zhang,Kathy N Williams,Charles A Peloquin,Sandeep Tyagi,Andrew A Vernon,William R Bishai,Richard E Chaisson,Jacques H Grosset,Eric L Nuermberger,Ian M Rosenthal,Ming Zhang,Kathy N Williams,Charles A Peloquin,Sandeep Tyagi,Andrew A Vernon,William R Bishai,Richard E Chaisson,Jacques H Grosset,Eric L Nuermberger,

BACKGROUND: Availability of an ultra-short-course drug regimen capable of curing patients with tuberculosis in 2 to 3 mo would significantly improve global control efforts. Because immediate prospects for novel treatment-shortening drugs remain uncertain, we examined whether better use of existing drugs could shorten the duration of treatment. Rifapentine is a long-lived rifamycin derivative currently recommended only in once-weekly continuation-phase regimens. Moxifloxacin is an 8-methoxyfluoroquinolone currently used in second-line regimens. METHODS AND FINDINGS: Using a well-established mouse model with a high bacterial burden and human-equivalent drug dosing, we compared the efficacy of rifapentine- and moxifloxacin-containing regimens with that of the standard daily short-course regimen based on rifampin, isoniazid, and pyrazinamide. Bactericidal activity was assessed by lung colony-forming unit counts, and sterilizing activity was assessed by the proportion of mice with culture-positive relapse after 2, 3, 4, and 6 mo of treatment. Here, we demonstrate that replacing rifampin with rifapentine and isoniazid with moxifloxacin dramatically increased the activity of the standard daily regimen. After just 2 mo of treatment, mice receiving rifapentine- and moxifloxacin-containing regimens were found to have negative lung cultures, while those given the standard regimen still harbored 3.17 log10 colony-forming units in the lungs (p < 0.01). No relapse was observed after just 3 mo of treatment with daily and thrice-weekly administered rifapentine- and moxifloxacin-containing regimens, whereas the standard daily regimen required 6 mo to prevent relapse in all mice. CONCLUSIONS: Rifapentine should no longer be viewed solely as a rifamycin for once-weekly administration. Our results suggest that treatment regimens based on daily and thrice-weekly administration of rifapentine and moxifloxacin may permit shortening the current 6 mo duration of treatment to 3 mo or less. Such regimens warrant urgent clinical investigation.

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. Publishing Authors By Initials

IM Rosenthal,M Zhang,KN Williams,CA Peloquin,S Tyagi,AA Vernon,WR Bishai,RE Chaisson,JH Grosset,EL Nuermberger,IM Rosenthal,M Zhang,KN Williams,CA Peloquin,S Tyagi,AA Vernon,WR Bishai,RE Chaisson,JH Grosset,EL Nuermberger,IM Rosenthal,M Zhang,KN Williams,CA Peloquin,S Tyagi,AA Vernon,WR Bishai,RE Chaisson,JH Grosset,EL Nuermberger,

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Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: PLoS medicine

VOLUME: 4

Page Numbers: e344

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ISSN: 1549-1676

DAY: 28

MONTH: Dec

YEAR: 2007

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. Information

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LANGUAGE: eng

NlmUniqueID: 101231360

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