Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Center for Pharmacist Education, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
J Pharm Sci. 2021 May;110(5):2295-2300. doi: 10.1016/j.xphs.2021.02.014. Epub 2021 Feb 17.
Linezolid-induced thrombocytopenia is related to linezolid exposure, baseline platelet count and patient background. Although the relationship usually reflects the time of onset of thrombocytopenia, if the platelet maturation process is taken into account, the platelet decrease can be considered to have started at the beginning of treatment. To predict linezolid-induced thrombocytopenia, classification and regression tree (CART) analysis based on machine learning has been applied to identify predictive factors and cutoff values. We examined 74 patient data with or without linezolid-induced thrombocytopenia. Linezolid concentration and platelet count change, baseline platelet count, age, body weight and creatinine clearance estimate were evaluated as predictive factors for linezolid-induced thrombocytopenia. CART analysis selected the final tree containing two cutoff values: a platelet count reduction to less than 2.3% from baseline at 96 h after the initial dose and a linezolid concentration greater than or equal to 13.5 mg/L at 96 h after the initial dose. The targets for therapeutic intervention were concluded to be the linezolid concentration and the platelet change from baseline at 96 h after the initial dose. These cutoff values occur prior to the onset of thrombocytopenia and should be monitored to avoid linezolid-induced thrombocytopenia.
利奈唑胺引起的血小板减少症与利奈唑胺暴露、基线血小板计数和患者背景有关。虽然这种关系通常反映了血小板减少症的发病时间,但如果考虑到血小板成熟过程,则可认为血小板减少症在治疗开始时就已经开始。为了预测利奈唑胺引起的血小板减少症,已经应用基于机器学习的分类和回归树(CART)分析来确定预测因素和临界值。我们检查了 74 例有或没有利奈唑胺引起的血小板减少症的患者数据。评估了利奈唑胺浓度和血小板计数变化、基线血小板计数、年龄、体重和估计的肌酐清除率作为利奈唑胺引起的血小板减少症的预测因素。CART 分析选择了最终包含两个临界值的树:初始剂量后 96 小时内基线血小板计数减少 2.3%以下,以及初始剂量后 96 小时内利奈唑胺浓度大于或等于 13.5mg/L。治疗干预的目标是初始剂量后 96 小时内的利奈唑胺浓度和血小板从基线的变化。这些临界值发生在血小板减少症之前,应进行监测以避免利奈唑胺引起的血小板减少症。