Fungal infections continue to be a major problem in the management of immunocompromised patients. Despite its formidable toxicity and treatment failures,
amphotericin B is still the
drug of choice for most of these
infections. One strategy for reducing the toxicity of
amphotericin B and thus permitting administration of higher doses is that of using less toxic formulations. Entrapping
amphotericin B into
liposomes or binding it to other substances reduces its toxicity to host cells, whereas the selective binding of
amphotericin B to
ergosterol preserves its toxicity to fungal cells. Adding fungus-specific
antibodies to such
liposomes may further increase the efficiency of drug targeting. The initial unpublished data from controlled clinical trials of various liposomal preparations of
amphotericin B are less encouraging than anticipated, but additional trials are needed for a proper evaluation. Another strategy for improving efficacy of
amphotericin B is that of bringing it directly into contact with the body sites most likely to be infected. Intranasal delivery of
amphotericin B for prevention of invasive
aspergillosis has been evaluated in at least three different clinical trials with conflicting results; no controlled trials are available. Prophylactic administration of low doses of
amphotericin B as an
aerosol was the most effective of the regimens tested in an animal model of
pulmonary aspergillosis and was also judged to be effective in a clinical trial using historical controls. Independent of the route of administration, in both an animal model was various clinical studies, early administration of
amphotericin B was more effective than late administration.(ABSTRACT TRUNCATED AT 250 WORDS)