We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles. 1. Case Ms. B, a 68-year-old woman, presented at our outpatient clinic with intense lower foot pain and fever since a week. Clinical examination revealed the 3 first phalanges of the left foot painful, cyanotic, and swollen in the absence of palpable pulsus at the ventral and dorsal tibial arteries with concomitant fever (38.5°C) and tachycardia (110？bpm). A complete blood count showed elevated total number of white blood cells (21 × 109/L), consisted of 93% from neutrophil granulocytes. She was admitted to our hospital due to sepsis and possible diagnosis of infection of the ischemic left foot. Anamnestic history included advanced peripheral ischemic disease, diabetes mellitus type II, arterial hypertension, and major depression. The patient was receiving treatment with fentanyl transdermal patch 25？μg/h every 72？h since 10 days and amitriptyline 25？mg BD for depression. The low dose of amitriptyline 25？mg BD was maintained due to its antidepressant [1, 2] as well as analgesic effects on chronic pain [3–5] and especially painful diabetic limb [6–12]. During her stay in the medical ward, she was treated with empirical antibiotics including cloxacillin, 3rd generation beta-lactams, and aminoglycosides with an initial general improvement. However, at the 10th day patient had a new onset of high fever (38.7°C) and linezolid 600？mg every 12 hours was added to the treatment regimen and cloxacillin was stopped. Within the first 24 hours of antibiotic change treatment, the patient had a rapid clinical deterioration manifesting symptomatology of restlessness, diaphoresis, tremor, shivering, myoclonus, and high fever (40°C), as well as gradual mental status disorders with disorientation, confusion, and coma. The patient was intubated due to severe respiratory difficulties according to the criteria of our clinic, and transferred to the intensive care unit. Brain computerized tomography and lumbar puncture (LP) for the exclusion of central neural system (CNS) infection were unremarkable. The constellation of the above neurological and mental state features in the presence of serotonergic medication [13–15] and the abstinence
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