methylamphotericin-b and Demyelinating-Diseases

Conditioned mongrel dogs were given 30 i.v. injections of either AMB (amphotericin B, 0.75 mg/kg body weight), AME (amphotericin B methyl ester, 10 mg/kg body weight), or 5% glucose solution without antimicrobic. Severe loss of body weight and nephrotoxicity occurred with AMB; hepatic dysfunction resulted with AME; astrogliosis and pallor of the myelin were found in dogs given AME and 5% glucose solution.

Topics: Amphotericin B; Animals; Bone Marrow; Central Nervous System; Demyelinating Diseases; Dogs; Kidney

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