Published ahead of print on September 8, 2005, doi:10.1164/rccm.200507-1047OC Am. J. Respir. Crit. Care Med., Volume 172, Number 11, December 2005, 1452-1456 A more recent version of this article appeared on December 1, 2005
Submitted on July 6, 2005 Rifapentine, Moxifloxacin or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse ModelEric Nuermberger1*,1 Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA * To whom correspondence should be addressed. E-mail: enuermb{at}jhmi.edu.
Rationale: Priorities for developing improved regimens for treatment of latent TB infection include (1) developing shorter and/or more intermittently administered regimens that are easier to supervise; and (2) developing and evaluating regimens that are active against multidrug-resistant organisms. Objectives and Methods: Using a previously validated murine model that involves immunizing mice with Mycobacterium bovis BCG to augment host immunity before infection with virulent Mycobacterium tuberculosis, we evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential of the Mycobacterium leprae Hsp65 DNA vaccine to augment the activity of moxifloxacin. Measurements: Quantitative spleen CFU counts and the proportion of mice with culture-positive relapse after treatment. Main Results: Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6-9 months. Six-month daily combinations of moxifloxacin with pyrazinamide, ethionamide or ethambutol were more active than pyrazinamide plus ethambutol, a regimen recommended for latent TB infection after exposure to multidrug-resistant TB. The combination of moxifloxacin with the experimental nitroimidazopyran PA-824 was especially active. Finally, the Hsp65 DNA vaccine had no effect on CFU counts when given alone, but augmented the bactericidal activity of moxifloxacin. Conclusions: Together, these findings suggest that rifapentine, moxifloxacin and, perhaps, therapeutic DNA vaccination, have the potential to improve upon the current treatment of latent TB infection. Key words: tuberculosis, latency, rifapentine, moxifloxacin, DNA vaccine
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