IN-VITRO BACTERICIDAL AND IN-VIVO THERAPEUTIC ACTIVITIES OF A NEW RIFAMYCIN DERIVATIVE, KRM-1648, AGAINST MYCOBACTERIUM-TUBERCULOSIS

The in vitro and in vivo activities of a new rifamycin derivative, KRM -1648, against Mycobacterium tuberculosis H37Rv were compared with tho se of rifampin, Bactericidal activity was evaluated by using a silicon e-coated slide culture method, The MBC of KRM-1648 was 0.15 to 0.3 mu/ ml for 24 h of exposure, while that of rifampin was >160 mu g/ml under the same conditions, Against experimental murine tuberculosis, KRM-16 48 exhibited significant therapeutic effects, in terms of prolonged su rvival times for mice compared with those with rifampin treatment, eve n at lower doses, such as 1 and 3 mg/kg, At a dose of 3 mg/kg, KRM-164 8 was at least as effective as rifampin at 10 mg/kg, The combination o f KRM-1648 (3 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/k g) exhibited much more activity than did rifampin (10 mg/kg) plus ison iazid (3 mg/kg) plus ethambutol (10 mg/kg), These findings suggest tha t KRM-1648 is a promising candidate for the treatment of tuberculosis.