A standard dose of linezolid put patients with hepatic impairment at risk of overexposure

Abstract

Abstract Purpose: The purpose of this retrospective observational study conducted in patients with hepatic impairment was to determine the risk factors for linezolid overexposure and the relationship between it and thrombocytopenia.Methods: All enrolled patients received a standard dose of linezolid and underwent therapeutic drug monitoring. The Child-Pugh-Turcotte score was used to divide patients into three groups: mild, moderate, and severe hepatic impairment. The risk factors for linezolid overexposure (Cmin > 8 mg/L) and thrombocytopenia were examined using logistic regression. And the Kaplan-Meier curve was used to describe the association between linezolid overexposure and thrombocytopenia.Results: Seventy-seven patients were included. Patients with severe hepatic impairment had a substantially higher median Cmin of linezolid than those with mild (20.65 mg/L vs 5.51 mg/L, P < 0.001) or moderate (20.65 mg/L vs 6.70 mg/L, P = 0.001) hepatic impairment. Severe hepatic impairment was significantly associated with linezolid overexposure (OR 7.037, 95%CI 1.426-34.727, P = 0.017). In addition, Cmin > 8 mg/L was a significant predictor of linezolid-induced thrombocytopenia (OR 3.024, 95%CI 1.083 - 8.541, P = 0.035).Conclusion: Patients with hepatic impairment who received standard doses of linezolid are at greater risk of linezolid overexposure, which may lead to a higher incidence of thrombocytopenia.