ACTIVITIES OF LIPOSOME-ENCAPSULATED AZITHROMYCIN AND RIFABUTIN COMPARED WITH THAT OF CLARITHROMYCIN AGAINST MYCOBACTERIUM-AVIUM-INTRACELLULARE COMPLEX IN HUMAN MACROPHAGES

The activities of liposome-entrapped azithromycin, rifabutin or clarit hromycin against Mycobacterium avium-intracellulare (MAI) were evaluat ed in a cell model of intramacrophage infection. Exposure of free (une ncapsulated) and liposome-encapsulated rifabutin or azithromycin to hu man monocyte-derived macrophages resulted in a marked increase in the uptake of the liposome-entrapped drugs compared to the free form. The macrophages were infected at day 7 of culture with MAI. Treatment was initiated 24 h following the infection and the surviving intracellular bacteria were counted at days 2, 4, and 5. The drugs were used at con centrations close to the serum peak levels achievable following admini stration of therapeutic oral doses. The antimycobacterial activity of each of the three drugs was significantly enhanced (P<0.01) when the d rugs were delivered in the liposome-entrapped form as compared with th e effects of the free drugs. Free and liposome-encapsulated drugs were used at the same concentrations. With the strain of MAI used (ATCC 49 601), the efficacy of clarithromycin was significantly higher (P<0.01) compared to free or liposome-entrapped azithromycin. Also, rifabutin either in the free or liposomal form, was markedly more effective than clarithromycin, Addition of ethambutol enhanced the efficacies of the three drugs whether in the free or liposomal forms. These results sug gest that liposome-encapsulation of rifabutin, azithromycin or clarith romycin may provide the means for effective eradication of MAI infecti ons. Further experiments in animal models are required to establish th e in vivo anti-MAI efficacy of these liposomal antimicrobials.