We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model.
- Authors
Rosenthal, Ian M; Zhang, Ming; Williams, Kathy N; Peloquin, Charles A; Tyagi, Sandeep; Vernon, Andrew A; Bishai, William R; Chaisson, Richard E; Grosset, Jacques H; Nuermberger, Eric L
- Abstract
<bold>Background: </bold>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.<bold>Methods and Findings: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
LUNG microbiology; DRUG therapy for tuberculosis; TUBERCULOSIS microbiology; DISEASE relapse prevention; ANIMAL experimentation; ANTIBIOTICS; ANTITUBERCULAR agents; BACTERIAL growth; BIOLOGICAL models; COMBINATION drug therapy; DRUG administration; ISONIAZID; LUNGS; MICE; MICROBIOLOGICAL techniques; MYCOBACTERIUM tuberculosis; ORGANIC compounds; QUINOLINE; QUINOLONE antibacterial agents; RESEARCH funding; RIFAMPIN; TIME; PYRAZINAMIDE
- Publication
PLoS Medicine, 2007, Vol 4, Issue 12, pe344
- ISSN
1549-1277
- Publication type
journal article
- DOI
10.1371/journal.pmed.0040344