Therapeutic efficacy of liposomal clofazimine against Mycobacterium avium complex in mice depends on size of initial inoculum and duration of infection

Abstract

The therapeutic efficacy of liposomal clofazimine (L-CLF) against Mycobacterium avium complex (MAC) was evaluated in the acute and chronic infection models of the beige mouse (C57BL/6J bg(j) bg(j)). The maximum tolerated dose of L-CLF was inversely proportional to the infection level. L- CLF showed higher antibacterial activity than free clofazimine. Treatment with 25 mg of L-CLF per kg of body weight (intravenously) was started at days 1, 8, 15, and 22 postinfection and was studied at three levels of MAC infection (104, 105, and 106 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 infection levels, irrespective of time of treatment. However, the best results were obtained when an already established infection was treated (day 22). The organ-related differences in response to the treatment were 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 higher infection levels. These studies might help in evaluations of host responses to therapy.