Antifungal Drugs


Encephalopathy, occasionally with parkinsonian features, can be associated with intravenous administration of amphotericin B. Autopsy examination of afflicted patients discloses diffuse noninflammatory degeneration of the white matter, characterized by demyelination and infiltration by foamy macrophages. The leukotoxic effect of amphotericin B is related to its binding to myelin and an increase in membrane permeability, resulting in leakage of intracellular components. y Clinically, the patients develop a subacutely evolving neurological disorder characterized by personality change and confusion, rapidly progressing to akinetic mutism. Neuroimaging studies disclose diffuse nonenhancing lesions of the cerebral white matter that include hypodensity on computed tomography (CT) and increased signal on T2 -weighted MRI. Amphotericin-associated leukoencephalopathy can be fatal, although there have been cases of slow recovery after discontinuation of the drug.


The incidence of neurotoxicity from parenteral polymyxin B averages 7 percent. Polymyxin has both presynaptic and postsynaptic effects, and it can worsen neuromuscular weakness, leading to respiratory failure, particularly in patients with renal failure or in combination with other drugs known to block neuromuscular transmission.^ The various adverse effects of polymyxins include paresthesias, peripheral neuropathy, diplopia, dysphagia, ototoxicity, muscle weakness, dizziness, ataxia, seizures, and confusion.^1 , y

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