肾功能不全对利奈唑胺代谢物浓度及血小板减少的影响分析

目的:探讨肾功能对利奈唑胺谷浓度及代谢物PNU-142300浓度的影响,评估利奈唑胺谷浓度及PNU-142300浓度对血小板减少(linezolid induced-thrombocytopenia,LIT)的影响及预警价值。方法:收集2019年11月至2022年1月在南京医科大学附属苏州医院住院期间使用利奈唑胺的患者,分为肾功能不全组与肾功能正常组,比较2组利奈唑胺谷浓度和PNU-142300浓度的差异,分析不同利奈唑胺谷浓度下LIT的发生风险。绘制受试者工作特征(receiver operation characteristic,ROC)曲线,评估利奈唑胺谷浓度及PNU-142300浓度对LIT的预警价值。结果:共收集92例患者,肾功能不全组40例,肾功能正常组52例。肾功能不全组利奈唑胺谷浓度及PNU-142300浓度更高(P＜0.01;P＜0.01),两者与肾功能均存在一定的负相关(Spearman's r=-0.371,P＜0.01;Spearman's r=-0.451,P＜0.01)。共19例患者发生LIT,肾功能不全组12例(30.00%),肾功能正常组7例(13.46%),差异无统计学意义(P=0.052)。利奈唑胺谷浓度≥7mg·L^-1相比于＜7mg·L^-1发生LIT的风险增加(Log-Rank P=0.010);肾功能不全者LIT风险增加(Log-Rank P=0.036)。LIT组利奈唑胺谷浓度和PNU-142300浓度更高(P＜0.01)。利奈唑胺谷浓度和PNU-142300浓度折点分别为12.10mg·L^-1、4.63mg·L^-1。结论:肾功能不全者利奈唑胺谷浓度及PNU-142300浓度更高。利奈唑胺谷浓度＞12.10mg·L^-1、PNU-142300浓度＞4.63mg·L^-1时LIT发生风险增加。

Analysis on the influence ofrenal insufficiency to the linezolid metabolite concentration and linezolid induced thrombocytopenia

OBJECTIVE To explore the effect of renal function on linezolid trough concentration and metabolite PNU-142300 concentration,and to evaluate the influence and predictive value of linezolid and metabolite PNU-142300 concentration on linezolid induced-thrombocytopenia(LIT).METHODS Patients who received linezolid treatment were retrospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University.Patients were divided into two groups according to their renal function.Linezolid trough concentrations and its metabolite PNU-142300 concentration were compared,and the correlation between the risk of LIT with linezolid or PNU-142300 concentrations were analyzed.Receiver operation characteristic(ROC)curve of the two groups were drawn to evaluate the predictive value of linezolid trough concentration and its metabolite PNU-142300concentration on LIT.RESULTS Totally 92 patients were included,with 40 cases of renal insufficiency and 52 cases of normal renal function.The linezolid trough concentration and the metabolite PNU-142300 concentration of patients with renal insufficiency were both higher than those of the normal renal function group(P<0.01;P<0.01).Both of them are negatively correlated with renal function(Spearman’s r=-0.371,P<0.01;Spearman’s r=-0.451,P<0.01).LIT occurred in 19 patients,including 12 patients(30.00%)in renal insufficiency group and 7 patients(13.46%)in normal renal function group,the difference between the two groups did not reach statistical significance(P=0.052).The risk of LIT was increased when linezolid trough concentration more than 7 mg·L^-1(Log-Rank P=0.010)or had renal insufficiency(Log-Rank P=0.036).Linezolid trough concentration and its metabolite PNU-142300 concentration in LIT group were higher than those in non-LIT group(P<0.01).The cut-off point of linezolid trough concentration and PNU-142300 concentration was 12.10 mg·L^-1 and 4.63 mg·L^-1.CONCLUSION The trough concentrations of linezolid and PNU-142300 in patients with renal insufficiency were significantly higher than those in patients with normal renal function.The risk of LIT increased when the trough concentration was>12.10 mg·L^-1 and PNU-142300 concentration was>4.63 mg·L^-1.