Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis.
In a recent experimental study using the mouse model of tuberculosis, treatment with a combination of rifampin, moxifloxacin, and pyrazinamide was able to shorten the time to negative lung cultures by up to 2 months compared with the standard regimen of rifampin, isoniazid, and pyrazinamide. To confirm that this substitution of moxifloxacin for isoniazid permits a shorter duration of treatment, a second study was performed in which mice were assessed for relapse after treatment with combination therapy for 3, 4, 5, or 6 months. Although no relapse was observed among mice treated for at least 4 months with rifampin, moxifloxacin, and pyrazinamide, mice treated with rifampin, isoniazid, and pyrazinamide required 6 months of treatment before no relapse could be detected. For mice treated with rifampin, moxifloxacin, and pyrazinamide, similar efficacy was noted whether pyrazinamide was administered for 1 month, 2 months, or the entire duration of therapy. These results suggest that the use of rifampin, moxifloxacin, and pyrazinamide may substantially shorten the duration of therapy needed to cure human tuberculosis and that the full benefit of pyrazinamide in this regimen may be realized after just 1 month of treatment.
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. enuermb@jhmi.edu
Eric L
EL
Nuermberger
Tetsuyuki
T
Yoshimatsu
Sandeep
S
Tyagi
Kathy
K
Williams
Ian
I
Rosenthal
Richard J
RJ
O'Brien
Andrew A
AA
Vernon
Richard E
RE
Chaisson
William R
WR
Bishai
Jacques H
JH
Grosset
D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D015999:Multivariate Analysis; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin