Introduction: Linezolid is an oxazolidinone antibiotic with a reversible, non-selective monoamine oxidase inhibitory effect. Combining linezolid with serotonergic agents may increase serotonin syndrome (SS) risk. Secondary to its high tissue penetration, linezolid is recommended in patients with suspected or confirmed resistant gram-positive bacterial infections, as pneumonia, and skin-soft tissue infections, especially if vancomycin cannot be used. However, it is unclear whether

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... on of linezolid with opioids increases the risk of serotonin syndrome. Research objective: Whether combing linezolid with opioids will increase the incidence of SS in acutely ill patients. Methods: This was a retrospective observational study. All adult patients admitted to Hamad Medical Corporation facilities in Qatar and received linezolid between March 2020 and September 2020 were included in the study. The primary outcome was the prevalence of SS defined by Hunter's criteria. SS was confirmed if the patient had spontaneous clonus; inducible clonus plus agitation or diaphoresis; ocular clonus plus agitation or diaphoresis; tremor plus hyperreflexia; or hypertonia plus fever plus ocular clonus or inducible clonus. Results: We included 106 patients, most of the patients were males (91.5%). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one patient (1.6%) had spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made the association with the linezolid-opioids combination doubtful. Conclusion: In this study, the incidence of SS was low in acutely ill patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.