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Free Content Activity of KRM 1648 or rifabutin alone or in combination with clarithromycin against Mycobacterium avium complex in human alveolar macrophages

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SETTING: The activity of KRM 1648 (KRM), a new benzoxazinorifamycin, and rifabutin (RBT), alone or in combination with clarithromycin (CLA), was evaluated against Mycobacterium avium complex (MAC) that multiplied in human alveolar macrophages (AM).

DESIGN: AM were recovered by bronchoalveolar lavage, incubated in RPMI 1640 medium with 10% human AB serum, infected with four strains of MAC (of non-acquired immune deficiency syndrome [AIDS] origin), and then treated with each drug alone or in combination. After incubation for 7 days, colony forming units in each well were counted on 7H10 agar.

RESULTS: Although concentrations between 0.2 μg/ml and 20 μg/ml of both rifamycins showed clear dose-dependent activities against all MAC strains tested, only 20 μg/ml of each drug had modest bactericidal effect. In combination with 2.0 μg/ml of CLA, however, 0.2 μg/ml of both drugs caused a bactericidal response against two of the four MAC strains examined.

CONCLUSION: According to this human alveolar macrophage model of MAC infection, KRM and RBT in combination with CLA was found to be a promising candidate against human pulmonary MAC infection, and deserves clinical evaluation.
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Keywords: KRM 1648; MAC; clarithromycin; human alveolar macrophage; rifabutin

Document Type: Regular Paper

Affiliations: Department of Infection and Inflammation, Chest Disease Research Institute, Kyoto University, Sakyo-ku Kyoto, Japan

Publication date: 1997-10-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

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