Linezolid interaction with serotonin reuptake inhibitors: report of two cases and incidence assessment.

BACKGROUND: Prompted by the advent of potentially life-threatening neuromuscular symptoms following initiation of linezolid therapy in two patients receiving treatment with a serotonin reuptake inhibitor antidepressant, an evaluation was conducted to determine the incidence and characteristics of symptomatic serotonin toxicity among hospitalized patients receiving combined treatment with these medications. METHODS: Patients admitted between January 1, 2006 and August 30, 2008 who received linezolid concurrently with citalopram or escitalopram were identified and their medical records were examined. Patients were judged to have serotonin toxicity if their records contained documentation of clinical evidence adequate to fulfill requisites of the Hunter Serotonin Toxicity Criteria. Severity of serotonin-related symptoms was graded according to previously established criteria. RESULTS: During the period of observation, 24 patients received concurrent treatment with linezolid and citalopram or escitalopram. Of these, one patient (4%) treated with citalopram met evidentiary requirements for diagnosis of serotonin toxicity. The severity of symptoms in this patient was graded as mild. No evidence of serious harm related to a possible drug interaction was identified. CONCLUSIONS: Severe symptoms associated with serotonin toxicity were shown to be uncommon in patients receiving linezolid and selected serotonin reuptake inhibitors. Nonetheless, serious interaction-related toxicity has been observed at our institution and reported in detail by others. Accordingly, concurrent use of these medications is categorized as contraindicated. Alternative antimicrobial therapy should be instituted in most cases. If no suitable alternative is available, recipient patients should be hospitalized for expectant observation and rigorous monitoring.

Implementing standardized intravenous antibiotic desensitizations among hospital inpatients.

PURPOSE: Patient safety improvements and increased efficiencies achieved through the establishment of standardized protocols and order sets for selected antibiotic desensitization procedures are described. SUMMARY: Errors in the ordering and administration of antimicrobial desensitization regimens can result in life-threatening complications. To enhance patient safety, the University of Colorado Hospital pharmacy department worked with allergy and immunology physicians (AIPs) to implement standardized desensitization protocols to reduce the potential for confusion surrounding the prescribing and administration of these complex regimens to acutely ill populations such as patients with cystic fibrosis, as many as 30% of whom develop one or more antimicrobial allergies. Nine i.v. antibiotics were identified as suitable for the standardization initiative; based on AIP experience and published guidelines, therapeutic doses of each targeted medication were determined. For each of the nine drugs, the interdisciplinary team developed an instruction sheet on preparing stock concentrations and compounding sequential doses for desensitization, with a corresponding preprinted order set detailing infusion procedures, monitoring requirements, guidance on the use of rescue medications and other steps for managing adverse reactions, and patient safeguards. Initial experience with the standardized protocols indicated that relative to previous practices (i.e., physician submission of handwritten patient-specific orders, with pharmacist calculation of required dilutions case by case), the standardization initiative (1) reduced the potential for errors, (2) sharply reduced order-entry and product preparation times, and (3) helped achieve antimicrobial stewardship goals. CONCLUSION: Standardized antimicrobial desensitization protocols helped to optimize patient care and antimicrobial stewardship while enabling more efficient use of pharmacy and AIP resources and fostering enhanced pharmacist-physician collaboration.