Treatment of Mycobacterium avium-intracellulare Complex Infection in Beige Mice with Free and Liposome-Encapsulated Streptomycin: Role of Liposome Type and Duration of Treatment

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Abstract
Current treatments for Mycobacterium avium-intracellulare complex (MAC) infections are generally ineffective. Thus, the potential of free or liposome-encapsulated streptomycin to treat acute MAC infection was investigated in beige mice. Free streptomycin administered intramuscularly 5 days a week (150 mg/kg) was effective in the liver, spleen, and lungs. At 4 weeks, liposome encapsulated streptomycin, administered intravenously in weekly doses (15 mg/kg), reduced the colony-forming units in the liver and spleen by about the same extent as a 50- to 100-fold higher dose offree drug. With 4 weekly injections ofliposomes, the colony-forming units in the liver and spleen were lower by 2.4 and 2.9 log units, respectively, compared to untreated controls, even by the end of 12 weeks. The effects of unilamellar and multilamellar liposomes were similar. These observations suggest that liposome encapsulation not only targets streptomycin to infected cells but also increases the residual activity of the drug.

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