An evaluation of linezolid-associated serotonin toxicity in combination with serotonergic agents at a community teaching hospital

PURPOSE: The purpose of this study was to assess demographic and clinical characteristics and potential risk factors for linezolid-associated serotonin toxicity in patients receiving linezolid and concomitant serotonergic agents. METHODS: This was a single-center, retrospective, single-cohort study. Adults at least 18 years of age who were ordered linezolid from January 1, 2014, through October 31, 2023, were screened for inclusion. Patients were included if they received at least one dose of linezolid and a concomitant serotonergic agent. Patients were excluded if the medications were administered more than 24 hours apart or if the patient was pregnant or lactating. All concomitant serotonergic agents were assessed and assigned a dose category based on typical dosing ranges for FDA-approved indications. Serotonin toxicity was assessed utilizing data from the electronic medical record and was defined according to the Sternbach or Hunter criteria. RESULTS: Of the 615 patients screened, 227 adults met the inclusion criteria with administration of linezolid and a concomitant serotonergic agent. The mean age was 62.4 years, and the mean duration of linezolid treatment was 5.5 days. Most patients were administered only one concomitant medication (59.9%), and most were classified as receiving a low dose (69.1%). Only 2 patients (0.9%) were identified with possible serotonin toxicity as defined by the Sternbach or Hunter criteria, with one case possibly associated with linezolid. CONCLUSION: The incidence of serotonin toxicity in hospitalized patients receiving linezolid with concomitant serotonergic agents was low in our study. Linezolid is likely safe in patients receiving select concomitant agents.