Activities of liposome-encapsulated azithromycin and rifabutin compared with that of clarithromycin against Mycobacterium avium-intracellulare complex in human macrophages.
The activities of liposome-ebtrapped azithromycin, rifabutin or clarithromycin against Mycobacterium avium-intracellullare (MAI) were evaluated in a cell model of intramacrophage infection. Exposure of free (unencapsulated) and liposome-encapsulated rifabutin or azithromycin to human 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 concentrations close to the serum peak levels achievable following administration of therapeutic oral doses. The antimycobacterial activity of each of the three drugs was significantly enhanced (P < 0.01) when the drugs were delivered in the liposome-entrapped form as compared with the effects of the free drugs. Free and liposome-encapsulated drugs were used at the same concentrations. With the strain of MAI used (ATCC 49601), the efficacy of clarithromycin was significantly bigher (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 suggest that liposome-encapsulation of rifabutin, azithromycin or clarithromycin may provide the means for effective eradication of MAI infections. Further experiments in animal models are required to establish the in vivo anti-MAI efficacy of these liposomal antimicrobials.
Onyeji
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CO
Department of Pharmacy and Research, Hartford Hospital, Hartford, CT 06115, USA.
Nightingale
C H
CH
Nicolau
D P
DP
Quintiliani
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