EFFICACIES OF LIPOSOME-ENCAPSULATED CLARITHROMYCIN AND OFLOXACIN AGAINST MYCOBACTERIUM-AVIUM MYCOBACTERIUM-INTRACELLULARE COMPLEX IN HUMAN MACROPHAGES

The therapeutic efficacies of liposome-encapsulated ofloxacin and clar ithromycin against Mycobacterium avium-M. intracellulare (MAI) were ev aluated in a model of intramacrophage infection. Liposome encapsulatio n was found to markedly enhance the uptake of each of the drugs by hum an macrophages. The human blood-derived macrophages were infected at d ay 7 of culture with MAI. Treatment was initiated 24 h after the infec tion, and the number of intracellular bacteria was determined at days 2, 3, and 4. Liposome entrapment of either ofloxacin or clarithromycin significantly (P < 0.005) enhanced the activities of the drugs when c ompared,vith the antimycobacterial effects of equivalent concentration s of the free (unentrapped) drugs. The drugs were used at concentratio ns close to their clinically achievable peak levels. The efficacy of c larithromycin, either in the free or liposome-entrapped form, was mark edly higher than that of ofloxacin. Liposome-encapsulated ofloxacin or clarithromycin plus ethambutol was, in each case, more effective in o rganism eradication (P < 0.005) than each agent used singly. These res ults suggest that liposome-encapsulated clarithromycin may be more eff ective than the free form of the drug against MAI infections in vivo, and the use of a combination therapy with ethambutol could further enh ance the efficacy.