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

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 r...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2004-02, Vol.169 (3), p.421-426
Main Authors: Nuermberger, Eric L, Yoshimatsu, Tetsuyuki, Tyagi, Sandeep, O'Brien, Richard J, Vernon, Andrew N, Chaisson, Richard E, Bishai, William R, Grosset, Jacques H
Format: Article
Language:English
Subjects:
Analysis of Variance
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Antitubercular Agents - pharmacology
Aza Compounds - pharmacology
Biological and medical sciences
Biological Availability
Culture Media
Disease Models, Animal
Drug Therapy, Combination
Female
Fluoroquinolones
Intensive care medicine
Medical sciences
Mice
Mice, Inbred BALB C
Microbial Sensitivity Tests
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Probability
Quinolines - pharmacology
Sensitivity and Specificity
Time Factors
Treatment Outcome
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Summary: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.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.200310-1380OC