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The in vitro and in vivo activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis H37Rv were compared with those of rifampin. Bactericidal activity was evaluated by using a silicone-coated slide culture method. The MBC of KRM-1648 was 0.15 to 0.3 microgram/ml for 24 h of exposure, while that of rifampin was &gt; 160 microgram/ml under the same conditions. Against experimental murine tuberculosis, KRM-1648 exhibited significant therapeutic effects, in terms of prolonged survival times for mice compared with those with rifampin treatment, even at lower doses, such as 1 and 3 mg/kg. At a dose of 3 mg/kg, KRM-1648 was at least as effective as rifampin at 10 mg/kg. The combination of KRM-1648 (3 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg) exhibited much more activity than did rifampin (10 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg). These findings suggest that KRM-1648 is a promising candidate for the treatment of tuberculosis.

In vitro bactericidal and in vivo therapeutic activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis