Possibly linezolid-induced peripheral and central neurotoxicity : Report of four cases

Background: Linezolid is the first member of the new synthetic class of antibacterial agents that prevent the formation of the 70S ribosomal subunit. It represents an attractive choice in the therapeutic arsenal because it is effective against methicillin-resistant strains of Staphylococcus spp. Adverse hematological events have been reported. They are rapidly reversible after discontinuation of treatment and usually occur during treatment courses of more than 2 weeks. The advised duration of linezolid use is 28 days and the consequences of prolonged use are unknown. In addition, this drug has some dopaminergic properties that can induce the serotonin syndrome if a monoamine oxidase inhibitor is used simultaneously. Patients and Methods: Since linezolid became available for use in 2002, four cases of probable central and peripheral linezolid-induced neurotoxicity have been recorded in our unit. Results: Two de novo peripheral neuropathies and one worsening of a preexisting toxic neuropathy have been observed. In each case, Linezolid therapy was used during a prolonged duration of 8, 23, and 24 weeks, respectively. First neurological signs appeared in one case during the 2nd week of treatment and beyond the 1st month in the other cases. To date, all cases of peripheral neuropathy resulted in persistent neurological damage after discontinuation of linezolid. Assessments did not reveal any other explanation for these neurological impairments. Another case concerned a patient who developed transient encephalopathy attributed to linezolid during a coadministration with hydroxyzine. Conclusion: Linezolid may induce persistent peripheral neuropathy after prolonged use and may cause a transient central neurotoxicity in combination with an anticholinergic agent, such as an antihistamine. Close neurological monitoring should be recommended in prolonged linezolid therapy and coadministration of a serotonin reuptake inhibitor or antihistamine should be avoided to limit neurological adverse events.