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 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. 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.
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 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. CONCLUSION: According to this human alveolar macrophage model of MACinfection, KRM and RBT in combination with CLA was found to be a promising candidate against humanpulmonary MAC infection, and deserves clinical evaluation.
Authors: K Suzuki; T Kimoto; K Tsuyuguchi; H Matsumoto; A Niimi; E Tanaka; T Murayama; R Amitani Journal: J Clin Microbiol Date: 1998-09 Impact factor: 5.948