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Antimicrobial Agents and Chemotherapy, Jun 1996, 1482-1485, Vol 40, No. 6
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM- 1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages

N Mor, B Simon and L Heifets
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.

Inhibitory and bactericidal activities of KRM-1648 were determined against Mycobacterium tuberculosis and M. avium residing in human monocyte-derived macrophages and extracellular M. tuberculosis and M. avium. MICs and MBCs of KRM-1648 against intracellular and extracellular bacteria were substantially lower than those of rifampin. The MICs and MBCs of either drug against the intracellular bacteria were only twofold lower than or equal to the values found for extracellular bacteria. The prolonged effect of KRM-1648 found in this study is probably associated with high ratios of intracellular accumulation, which were 50- to 100-fold higher than that found for rifampin. Further studies on intracellular distribution of KRM-1648 and on the sites of actual interaction between the drug and bacteria residing in macrophages are necessary, as well as evaluation of combined effects of KRM-1648 with other drugs in long-term macrophage culture experiments.


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