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

Abstract

Purpose The purpose of this retrospective observational study conducted in patients with hepatic impairment was to assess the variability of linezolid trough concentrations, to determine the risk factors for linezolid overexposure, and to investigate the effect of linezolid overexposure on linezolid-induced thrombocytopenia. Methods All enrolled patients received a standard dose (600 mg every 12 h) 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 (C_min > 8 mg/L) and linezolid-induced thrombocytopenia were examined using logistic regression. And the Kaplan–Meier curve was used to describe the association between linezolid overexposure and linezolid-induced thrombocytopenia. Results Seventy-seven patients were included, 37 (48.1%) of whom experienced linezolid overexposure. Patients with severe hepatic impairment had a substantially higher median C_min of linezolid than those with mild (20.7 mg/L vs 5.51 mg/L, P < 0.001) or moderate (20.7 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). After linezolid treatment, linezolid-induced thrombocytopenia occurred in 32 (41.6%) patients, and C_min > 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 linezolid-induced thrombocytopenia.