基于治疗药物监测的重症患者哌拉西林他唑巴坦PK/PD研究

目的：探索临床使用哌拉西林他唑巴坦的重症感染患者首次治疗药物监测（TDM）后的峰谷浓度及PK/PD参数达标情况。方法：采用高效液相色谱法测定患者哌拉西林血药浓度，以本研究组建立的简易数学模拟法为基础，分别计算fT_>MIC ≥ 50%及100%的比例，并分析不同MIC值下各PK/PD目标值的达标情况。结果：58例患者的首次谷浓度为（31.68±44.33）μg·mL^-1，峰浓度为（206.59±101.37）μg·mL^-1，有5例（8.6%）患者首次谷浓度超过5 MIC，患者个体间变异较大；fT_>MIC ≥ 50%及100%的达标率分别为62.07%和36.21%。58例患者中7例确认为哌拉西林他唑巴坦耐药病原菌感染（MIC ≥ 128 μg·mL^-1），当按耐药菌的最低MIC值（128 μg·mL^-1）计算时，其fT_>MIC ≥ 50%及100%的达标率仅为28.57%和0。结论：有必要在重症感染患者中开展基于TDM的哌拉西林他唑巴坦个体化给药方案设计。

Pharmacokinetic/pharmacodynamic analysis of piperacillin/tazobactam in critically ill patients by therapeutic drug monitoring (TDM)

OBJECTIVE To explore serum concentrations and PK/PD parameters of piperacillin/tazobactam after first therapeutic drug monitoring (TDM) in critically ill patients.METHODS Serum concentrations of piperacillin/tazobactam were determined using high performance liquid chromatography (HPLC),and a mathematical model was used to estimate individual pharmacokinetic parameters.The percentages of the fT_>MIC ≥ 50% and 100% were calculated,PK/PD parameters were analyzed at different minimum inhibitory concentrations (MIC).RESULTS Fifty eight patients were included,the first TDM trough concentration and peak concentration were (31.68±44.33)μg·mL^-1 and (206.59±101.37)μg·mL^-1,five (8.6%) patients had trough concentrations higher than 5×MIC.Target attainment rates for fT_>MIC ≥ 50% and 100% were 62.07% and 36.21%,respectively.For pathogens with MICs of ≥ 128 μg·mL^-1 (seven patients),target attainment rates for fT_>MIC ≥ 50% and 100% were 28.57% and 0.CONCLUSION Among critically ill patients,it is necessary to design individualized dosage regimen based on TDM.