LIPOSOMAL AMIKACIN FOR TREATMENT OF MYCOBACTERIUM-AVIUM INFECTIONS INCLINICALLY RELEVANT EXPERIMENTAL SETTINGS

In an effort to optimize rational chemotherapy against M. avium infect ions in a clinically meaningful context, we tested whether liposome-en capsulated amikacin would effectively reduce the bacterial load in (i) intravenously infected immunodeficient SCID mice, (ii) immunocompeten t mice in both early and late stages of intravenous infection, and (ii i) immunocompetent mice with pulmonary M. avium infection. Although co mplete eradication of M. avium was never achieved following intravenou s infection, mycobacterial CFUs decreased by 3 to 4 logs in the spleen s and livers of mice treated for three weeks with twice-weekly intrave nous injections of liposomal amikacin and continued to stay low in the liver, even in the absence of specific immunity. Mice treated in the chronic stage of infection equally benefited from therapy and showed s igns of attenuated granulomatous inflammation in the liver. Even morib und mice responded to liposomal amikacin by significantly gaining weig ht and survived their infected untreated littermates by at least 4 mon ths. In contrast, during pulmonary M. avium infection, treatment with liposome-encapsulated amikacin only resulted in a transient plateau of bacterial proliferation in the lungs, and the infection exacerbated i mmediately after cessation of therapy.