Rifapentine, moxifloxacin, or DNA vaccine improves treatment of latent tuberculosis in a mouse model.
BACKGROUND
Priorities for developing improved regimens for treatment of latent tuberculosis (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.


OBJECTIVE
By using a previously validated murine model that involves immunizing mice with Mycobacterium bovis bacillus Calmette-Guérin 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 heat shock protein-65 DNA vaccine to augment the activity of moxifloxacin.


METHODS
Quantitative spleen colony-forming unit counts, and the proportion of mice with culture-positive relapse after treatment, were determined.


RESULTS
Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6-9 mo. 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 heat shock protein-65 DNA vaccine had no effect on colony-forming unit 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 on the current treatment of latent TB infection.
Nuermberger
Eric
E
Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USA. enuermb@jhmi.edu
Tyagi
Sandeep
S
Williams
Kathy N
KN
Rosenthal
Ian
I
Bishai
William R
WR
Grosset
Jacques H
JH
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones; D005500:Follow-Up Studies; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011804:Quinolines / Q000627:therapeutic use*; D012293:Rifampin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D019444:Vaccines, DNA / Q000627:therapeutic use*
D000904:Antibiotics, Antitubercular; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D019444:Vaccines, DNA; D000077266:Moxifloxacin; D012293:Rifampin; C018421:rifapentine