Neurotoxicity in adult patients with cystic fibrosis using polymyxin B for acute pulmonary exacerbations

Abstract

We present four case reports that describe neurotoxicity experienced in adult patients with cystic fibrosis (CF) receiving intravenous polymyxin B. Paresthesia was observed after the first dose of polymyxin B in all patients. These symptoms resolved after discontinuation of polymyxin B and switching treatment to colistin. All four patients completed therapy with colistin without experiencing additional adverse reactions. This report contributes to the small body of literature currently available on the use of polymyxin B in the CF population.

Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses

“…Neurotoxicosis due to polymyxin administration is known in human medicine causing signs such as paresthesia, dizziness, ataxia, and apnea [13,19]. In healthy horses, we recently showed the development of ataxia and weakness due to PolyB administration [23].…”

“…Paresthesia is the most common sign of neurotoxicosis in humans and abnormal sensatory pathways might also explain ataxia in horses [13,19]. The pathomechanism of PolyB neurotoxicity is incompletely understood; while earlier study suggested a neuromuscular blockade by a reduced sensitivity of the motor end plate to acetylcholine, newer studies show neuronal oxidative stress and mitochondrial dysfunction in response to polymyxin administration in mice [14,20,25].…”

“…In this study, we detected a statistically significant negative effect of the time since the last dose on ataxia gradings displaying a decrease in severity after therapy was stopped. Severity of neurological deficits depends on the dose and duration of polymyxin administration and clinical signs are reversible after discontinuation of therapy in humans and healthy horses [13,19,23]. Further influencing factors on the development of neurological signs include other medications, primary disease, and pre-existing neurological abnormalities [13].…”

“…Factors increasing the risk for nephrotoxicity include the duration and dose of therapy, concomitant administration of other nephrotoxic medications, and pre-existing diseases [13]. Neurotoxicity, although less common, leads to paresthesia, dizziness, ataxia, and possibly life-threatening apnea in human patients [13,19]. Recent studies in mice indicate mitochondrial dysfunction in neurons, but pathophysiology is incompletely understood and other mechanisms such as a reduced sensitivity of the motor end plate to acetylcholine or calcium-dependent prolongation of neuronal depolarization have been proposed [14,20].…”