Patient Safety: Toxic Neuropathy Following Treatment With Linezolid

From the Quality and Patient Safety Committee

A 54-year-old man presented with a 4- week history of progressive loss of sensation and unsteadiness of gait. Four months earlier, he developed septic arthritis and was started on linezolid at 600 mg daily. After 3 months of linezolid treatment, he developed progressive sensory loss in lower extremities and ataxic gait. Examination showed length-dependent sensory loss to all modalities in distal lower and upper extremities, with hyporeflexia, positive Romberg sign and mildly unsteady gait. Initial laboratory testing included hemoglobin A1c at 5.7%, negative serum protein electrophoresis with immunofixation and normal vitamin B12 level. Electrodiagnostic testing revealed length-dependent axonal sensory>motor polyneuropathy with normal needle examination. Etiology of neuropathy was attributed to linezolid toxicity. After linezolid was discontinued, the progression of neuropathy stopped.

Question: The most significant risk factor for developing toxic neuropathy during treatment with linezolid is:

A. Prior history of alcohol abus
B. High dose treatment
C. Pre-existing diabetes
D. Prolonged treatment (>28 days)

Explanation: Linezolid is an oxazilidinone antibiotic used for treatment of drug resistant gram-positive bone and joint infections and multidrug resistant tuberculosis. Increasing drug resistance dictates more frequent use of second- and third-line therapies, including linezolid. Prolonged treatment courses longer than 28 days have been associated with peripheral neuropathy and optic neuropathy, and the toxicity was explained by inhibition of mitochondrial protein synthesis. It has been estimated that 13-38% of patients treated with linezolid for 9 to 26 weeks may develop peripheral neuropathy which may become irreversible with prolonged treatment in up to 78% of patients. The risk of neurotoxicity is primarily related to the length of treatment, and the individual treatment dose of linezolid (high vs low) and comorbidities (e.g. diabetes) have less impact on the risk of complications. Most common phenotypes of toxic neuropathy attributable to linezolid include sensory and sensorimotor axonal polyneuropathies, similarly as with some other toxic polyneuropathies. Early recognition of toxic neuropathy and discontinuation of neurotoxic medications increase the chance of symptom improvement.

Authors: Sasha Zivkovic, MD, PhD; Michael Wimmer, MD

Sources:

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