利奈唑胺谷浓度治疗药物监测的初步研究

The rapeutic drug monitoring of linezolid trough concentrations

目的初步研究利奈唑胺治疗革兰阳性球菌感染患者的谷浓度变化趋势及其相关影响因素。方法回顾性分析2015年1月-2017年6月间本院应用利奈唑胺治疗革兰阳性球菌感染的患者临床资料及治疗药物监测(TDM)结果。采用高效液相色谱法测定血浆利奈唑胺谷浓度。结果 102名患者共检测了216次利奈唑胺谷浓度,男性及女性患者间利奈唑胺谷浓度差异无统计学意义[男vs女:6.0mg·L-1(2.9~12.0 mg·L-1)vs 5.7 mg·L-1(3.1~10.9 mg·L-1);H=1.877,P=0.122];Logistic回归分析显示:与利奈唑胺谷浓度是否>8 mg·L-1独立相关的因素有年龄(OR=1.361,95%CI 1.117~1.529,P=0.039)及血清肌酐水平(OR=1.212,95%CI 1.015~1.407,P=0.007)。利奈唑胺第2次检测(第12日)时大于利奈唑胺谷浓度的治疗范围上限8 mg·L-1,之后随时间变化呈现逐渐升高趋势。结论老年人及肾功能受损患者易出现利奈唑胺过量,治疗药物监测可早期检测利奈唑胺过量,为减少不良反应的发生提供依据。

Objective To explore the variation of trough concentrations and related influencing factors of linezolid for infections from Gram-positive cocci in patients. Methods We retrospectively analyzed the clinical data and therapeutic drug monitoring results of patients with infections from Gram-positive cocci treated with linezolid in our hospital between Jan. 2015 and Jun. 2017. Trough concentrations of linezolid were monitored by the method of high performance liquid chromatography. Results Totally 102 patients with 216 trough concentrations of linezolid were monitored. No significant differences of trough concentrations of linezolid were found between the males and the females [6.0 mg L - 1 （2.9 - 12.0 mg L - 1） vs 5.7 mg L - 1 （3.1 -10.9 mg L - 1）; H = 1.877, P = 0.122]. Logistic regression showed age （OR= 1.361, 95%C1 1.117 - 1.529, P = 0.039） and serum creatinine （OR = 1.212, 95% C1 1.015 - 1.407, P = 0.007） were independently associated with whether linezolid trough concentrations 〉 8 mg L -1. The trough concentration increased with time at the second monitoring （Day 12 from the first linezolid use）, and the level of linezolid exceeded the upper therapeutic limit of 8 mg L- 1. Conclusion Patients with old age and renal insufficiency tend to be overexposed to linezolid. Therapeutic drug monitoring may detect early overexposure of linezolid, to help reduce the occurrence of adverse effects.