多重耐药革兰阴性菌感染患者多黏菌素B暴露量影响因素及PK/PD参数与疗效相关性  

Influencing Factors of Polymyxin B Exposure and the Correlation Between PK/PD Index and Efficacy in Patients with Multidrug-resistant Gram-negative Bacterial Infections

作　　者：周思敏 罗雪梅[3] 葛卫红[1,3] ZHOU Simin;LUO Xuemei;GE Weihong(Department of Pharmacy,Nanjing Drum Tower Hospital,China Pharmaceutical University,Nanjing 210008,China;School of Basic Medcine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China;Department of Pharmacy,Nanjing Drum Tower Hospital,Medical College,Nanjing University,Nanjing 210008,China)

机构地区：[1]中国药科大学南京鼓楼医院药学部,南京210008 [2]中国药科大学基础医学与临床药学学院,南京210009 [3]南京大学医学院附属鼓楼医院药学部,南京210008

出　　处：《医药导报》2025年第3期428-434,共7页Herald of Medicine

摘　　要：目的探究多重耐药革兰阴性菌(MDR-GNB)感染患者多黏菌素B暴露量的影响因素及药动学/药效学(PK/PD)参数与疗效的相关性。方法前瞻性收集2021年1月—2023年12月南京大学医学院附属鼓楼医院重症医学科使用多黏菌素B治疗MDR-GNB感染患者的临床资料;采用高效液相色谱-串联质谱法测定多黏菌素B血药浓度,分析影响多黏菌素B暴露量的因素;绘制受试者工作特征(ROC)曲线分析不同暴露参数24 h药物浓度-时间曲线下面积(AUC_(24 h))、AUC_(24 h)与最低抑菌浓度(MIC)比值对临床疗效的预测价值。结果96例MDR-GNB感染患者AUC_(24 h)中位数为76.11(56.06,96.94)μg·mL^(-1)·h。大剂量组(≥150 mg·d^(-1))多黏菌素B暴露量明显高于小剂量组(<150 mg·d^(-1))(P<0.05),肾脏替代治疗可导致暴露量显著降低(P<0.01),而接受肾脏替代治疗的患者增加剂量对暴露量无显著影响。ROC曲线显示AUC_(24 h)/MIC与MDR-GNB感染患者临床疗效关联性最强(AUC_(ROC)=0.724,P<0.01),且AUC_(24 h)/MIC预测临床疗效的最佳阈值为62.1。亚组分析显示,AUC_(24 h)/MIC预测肺部感染患者与非肺部感染的最佳阈值分别为70.8和61.5。AUC_(24 h)/MIC≥62.1组患者临床有效率明显高于AUC_(24 h)/MIC<62.1组(72.88%vs.32.43%,P<0.01)。治疗后,AUC_(24 h)/MIC≥62.1组炎症指标下降趋势也优于AUC_(24 h)/MIC<62.1组。结论给药剂量、肾脏替代治疗是影响多黏菌素B暴露量的重要因素。AUC_(24 h)/MIC≥62.1是预测多黏菌素B治疗MDR-GNB感染患者疗效的最佳暴露指标,而AUC_(24 h)/MIC预测肺部感染患者临床有效的临界值高于非肺部患者,推荐进行治疗药物监测调整AUC_(24 h)/MIC指标,实现个体化给药。Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC_(24 h))and AUC_(24 h)to minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC_(24 h)was 76.11(56.06,96.94)μg·mL^(-1)·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥150 mg·d^(-1))were more likely to have higher exposure of polymyxin B than those in the low-dose group(<150 mg·d^(-1))(P<0.05).The exposure in patients with renal replacement therapy was significantly decreased(P<0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC_(24 h)/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUC_(ROC)=0.724,P<0.01)and the optimal cut-off value of AUC_(24 h)/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC_(24 h)/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical efficacy rate was significantly higher in AUC_(24 h)/MIC≥62.1 group,compared with those in AUC_(24 h)/MIC<62.1 group(72.88%vs.32.43%,P<0.01).After treatment,the decreasing trend of inflammation indicators in AUC_(24 h)/MIC≥62.1 group was superior to those in AUC_(24 h)/MIC<62.1 group.Conclusion The dose and renal replacement

关 键 词：多黏菌素B 多重耐药革兰阴性菌 暴露量 药动学/药效学 影响因素 

分 类 号：R978.1[医药卫生—药品] R969[医药卫生—药学]