PMID: 9441102Jan 24, 1998Paper

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

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
K SuzukiF Kuze

Abstract

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