THERAPEUTIC EFFICACY OF LIPOSOMAL CLOFAZIMINE AGAINST MYCOBACTERIUM-AVIUM COMPLEX IN MICE DEPENDS ON SIZE OF INITIAL INOCULUM AND DURATION OF INFECTION

The therapeutic efficacy of liposomal clofazimine (L-CLF) against Myco bacterium avium complex (MAC) was evaluated in the acute and chronic i nfection models of the beige mouse (C57BL/6J bg(j) bg(j)), The maximum tolerated dose of L-CLF was inversely proportional to the infection l evel L-CLF showed higher antibacterial activity than free clofazimine, Treatment with 25 mg of L-CLF per kg of body weight (intravenously) w as started at days 1, 8, 15, and 22, postinfection and was studied at three levels of MAC infection (10(4), 10(5), and 10(6) bacilli/mouse), L-CLF treatment caused a significant (P < 0.05 to 0.001) reduction in the numbers of viable bacteria in lung, liver, and spleen at all infe ction levels, irrespective of time of treatment, However, the best res ults were obtained when an already established infection was treated ( day 22), The organ-related differences in response to the treatment we re also affected by the level of infection, A marked reduction in the numbers of CFU was observed in the lungs of mice with lower infection levels, whereas liver and spleen were treated more efficiently at high er infection levels, These studies might help in evaluations of host r esponses to therapy.