methylamphotericin-b and Coccidioidomycosis

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Coccidioidomycosis; Cryptococcosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycoses

Clinical and autopsy studies of 14 patients treated with amphotericin B methyl ester (AME) for focal, disseminated, and nervous system mycotic infections revealed a high incidence of progressive neurologic dysfunction (dementia, akinesia, mutism, hyperreflexia, and tremor) and diffuse white matter degeneration. All of seven patients who received greater than 9.8 g of AME intravenously developed severe neurologic and neuropathologic changes. Two of three patients given 5-7.2 g of AME developed less severe neurologic symptoms; all three had mild diffuse white matter gliosis. Four patients given less than 1.5 g of AME had no bran abnormalities except those related to coccidioidal meningitis. Thirty-one control patients who died on untreated or amphotericin B-treated coccidioidal meningitis showed no diffuse white matter abnormalities. These findings indicate that prolonged administration of AME and/or other contaminating polyenes injures human white matter. Long-term animal studies, with particular attention to nervous system histology, must precede human use of other polyene derivatives.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Astrocytes; Brain; Brain Diseases; Child; Coccidioidomycosis; Demyelinating Diseases; Gliosis; Humans; Lung Diseases, Fungal; Middle Aged; Myelin Sheath

Topics: Amphotericin B; Animals; Brain Diseases; Coccidioidomycosis; Dogs; Humans; Macaca mulatta; Mycoses; Nervous System Diseases