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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.

B P Kelly, S K Furney, M T Jessen, I M Orme
B P Kelly
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
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S K Furney
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
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M T Jessen
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
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I M Orme
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
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DOI: 10.1128/AAC.40.12.2809
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ABSTRACT

As a paradigm for chronic infectious diseases, tuberculosis exhibits a variety of clinical presentations, ranging from primary pulmonary tuberculosis to reactivation tuberculosis and cavitary disease. To date, the animal models used in evaluating chemotherapy of tuberculosis have been high-dose intravenous models that mimic the disseminated forms of the disease. In the present study, we have used a low-dose aerosol exposure model which we feel better reflects newly diagnosed tuberculosis in patients converting to tuberculin positivity. As appropriate examples of chemotherapy, four rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) were tested, first in an in vitro murine macrophage model and then in the low-dose aerosol infection model, for their activity against Mycobacterium tuberculosis. In both models, KRM-1648 had the highest level of activity of the four compounds. In the infected-lung model, rifabutin, rifapentine, and KRM-1648 all had sterilizing activity when given orally at 5 mg/kg of body weight per day. When given at 2.5 mg/kg/day, KRM-1648 had the highest level of activity of the four drugs, reducing the bacterial load by 2.7 logs over 35 days of therapy.

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Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.
B P Kelly, S K Furney, M T Jessen, I M Orme
Antimicrobial Agents and Chemotherapy Dec 1996, 40 (12) 2809-2812; DOI: 10.1128/AAC.40.12.2809

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Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.
B P Kelly, S K Furney, M T Jessen, I M Orme
Antimicrobial Agents and Chemotherapy Dec 1996, 40 (12) 2809-2812; DOI: 10.1128/AAC.40.12.2809
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