Activity of Rifabutin Alone or in Combination with Clofazimine or Ethambutol or Both Against Acute and Chronic Experimental Mycobacterium intracellulare Infections

Rifabutin (ansamycin LM 427) when given alone in doses of 5, 10, or 20 mg/kg showed limited in vivo activity against acute or chronic Mycobacterium intracellulare infections studied in beige C57B1/6, or S/W mice. Prophylactic studies in S/W mice in which chemotherapy was given for 3 wk prior to challenge showed slight improvement. Combination chemotherapy consisting of rifabutin (10 mg/kg) and clofazimine (20 mg/kg) achieved complete sterilization of M. intracellulare infections in spleen and lung when initiated immediately after challenge. Inclusion of ethambutol did not offer additional benefit. If chemotherapy is initiated 3 wk after challenge (established infections), the activity of this double drug combination is less effective.