IN-VITRO ACTIVITIES OF FREE AND LIPOSOMAL DRUGS AGAINST MYCOBACTERIUMAVIUM-M-INTRACELLULARE COMPLEX AND MYCOBACTERIUM-TUBERCULOSIS

We compared MICs and MBCs of various free- and liposome-incorporated a ntimicrobial agents against several patient isolates of Mycobacterium avium-M. intracellulare complex and certain American Type Culture Coll ection strains of M. avium, M. intracellulare, and Mycobacterium tuber culosis. Seven of 19 agents were selected for incorporation into lipos omes. The MICs of these agents for 50 and 90% of isolates tested (MIC( 50)s and MIC(90)s, respectively) ranged from 0.5 to 62 mu g/ml. Member s of the M. avium-M. intracellulare complex were resistant to killing by most of the other agents tested in the free form. However, clofazim ine, resorcinomycin A, and PD 117558 showed complete killing of bacter ia at concentrations ranging from 8 to 31 mu g/ml, represented as MBC( 90)s. Among the liposome-incorporated agents, clofazimine anti resorci nomycin A had the highest killing effects (MBC(90)s, 8 and 16 mu g/ml, respectively). Furthermore, both free and liposome-incorporated clofa zimine had equivalent growth-inhibitory and killing effects on all Ame rican Type Culture Collection strains of M. avium, M. intracellulare, and M. tuberculosis tested. These results show that the antibacterial activities of certain drugs, particularly those of clofazimine and res orcinomycin, were maintained after the drugs were incorporated into li posomes.