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Published ahead of print on August 11, 2004, doi:10.1164/rccm.200407-885OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 10, November 2004, 1131-1134

A more recent version of this article appeared on November 15, 2004
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Submitted on July 9, 2004
Accepted on August 10, 2004

Moxifloxacin-containing Regimens of Reduced Duration Produce a Stable Cure in Murine Tuberculosis

Eric L Nuermberger1*, Tetsuyuki Yoshimatsu1, Sandeep Tyagi1, Kathy Williams1, Ian Rosenthal1, Richard J O'Brien2, Andrew A Vernon3, Richard E Chaisson1, William R Bishai1, and Jacques H Grosset1

1 Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA, 2 Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland, 3 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: enuermb{at}jhmi.edu.

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 to 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. While 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 one month of treatment.
Key words: tuberculosis, moxifloxacin, fluoroquinolone, pyrazinamide, mouse




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