Polymyxins neurotoxic effect

During treatment with any of the polymyxins, neurotoxicity can occur in up to 7% of patients with normal renal function. Circumoral paresthesia, vasomotor instability, ataxia, dizziness, convulsions of varying severity, and apnea have been reported. Of 31 patients with cystic fibrosis 21 had one or more adverse effects attributed to colistin (14). The most common reactions involved reversible neurological effects, including oral and perioral paresthesia (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these effects, although bothersome, were benign and reversible. There was no relation between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetics. 

Several toxic side-effects have been reported when polymyxin B and colistin are administered parenterally. Besides local irritation and pain at the site of injection in intramuscular administration, marked nephrotoxic effects are observed manifested by proteinuria, and cylindruria accompanied occasionally by an increase in white, red and epithelical cells in the urinary sediment. The neurotoxic effects of the drugs are characterized by flushing of the face, drowsiness, and a feeling of weakness and irritability. These symptoms, however, are transitory and disappear upon removal of the drug. In patients with pre-existing renal damage polymyxin and colistin should be administered in lower doses under frequent control of the renal functions. The recently available sodium sulphomethyl derivatives of polymyxin B and colistin are stated to be less toxic, yet these derivatives are also less active than their parent compounds - . ... 

Polymyxin B sulfate, a polypeptide antibiotic, is effective against gram-negative organisms. Hypersensitivity to topically applied polymyxin is rare. To reduce the likelihood of neurotoxicity and nephrotoxicity the total daily dose applied to the denuded skin or to open wounds should not exceed 200 mg. 

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