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Published ahead of print on October 24, 2003, doi:10.1164/rccm.200310-1380OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 421-426, (2004)
© 2004 American Thoracic Society

Moxifloxacin-containing Regimen Greatly Reduces Time to Culture Conversion in Murine Tuberculosis

Eric L. Nuermberger, Tetsuyuki Yoshimatsu, Sandeep Tyagi, Richard J. O'Brien, Andrew N. Vernon, Richard E. Chaisson, William R. Bishai and Jacques H. Grosset

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia

Correspondence and requests for reprints should be addressed to Jacques H. Grosset, M.D., 1503 E. Jefferson Street, Baltimore, MD 21231-1002. E-mail: jgrosse4{at}jhmi.edu

Tuberculosis continues to be a major cause of morbidity and mortality in the world. The expansion of tuberculosis control programs has been limited by the lengthy and cumbersome nature of current chemotherapeutic regimens. A new drug that improves the sterilizing activity of current regimens would reduce the duration of therapy without sacrificing efficacy, thereby enhancing treatment completion rates and preserving precious public health resources. The new 8-methoxyfluoroquinolone moxifloxacin has potent activity against both actively multiplying and nonactively multiplying tubercle bacilli. Using a murine model that is representative of chemotherapy for human tuberculosis, we show that the combination of moxifloxacin, rifampin, and pyrazinamide reduced the time needed to eradicate Mycobacterium tuberculosis from the lungs of infected mice by up to 2 months when compared with the standard regimen of isoniazid, rifampin, and pyrazinamide. The findings suggest that this regimen has the potential to substantially shorten the duration of therapy needed to cure human tuberculosis.

Key Words: fluoroquinolone • mouse • moxifloxacin • treatment • tuberculosis




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