Activity of KRM 1648 or rifabutin alone or in combination with clarithromycin against Mycobacterium avium complex in human alveolar macrophages
Abstract: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.
Document Type: Regular Paper
Affiliations: Department of Infection and Inflammation, Chest Disease Research Institute, Kyoto University, Sakyo-ku Kyoto, Japan
Publication date: October 1, 1997
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