Abstract：
BACKGROUND: Several studies report lack of meropenem pharmacokinetic/pharmacodynamic (PK/PD) target attainment (TA) and risk of therapeutic failure with intermittent bolus infusions in intensive care unit (ICU) patients. The aim of this study was to describe meropenem TA in an ICU population and the clinical response in the first 72 h after therapy initiation.
METHODS: A prospective observational study of ICU patients ≥18 years was conducted from 2014 to 2017. Patients with normal renal clearance (NRC) and augmented renal clearance (ARC) and patients on continuous renal replacement therapy (CRRT) were included. Meropenem was administered as intermittent bolus infusions, mainly at a dose of 1 g q6h. Peak, mid, and trough levels were sampled at 24, 48, and 72 h after therapy initiation. TA was defined as 100% T > 4× MIC or trough concentration above 4× MIC. Meropenem PK was estimated using traditional calculation methods and population pharmacokinetic modeling (P-metrics®). Clinical response was evaluated by change in C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, leukocyte count, and defervescence.
RESULTS: Eighty-seven patients were included, with a median Simplified Acute Physiology (SAPS) II score 37 and 90 days mortality rate of 32%. Median TA was 100% for all groups except for the ARC group with 45.5%. Median CRP fell from 175 (interquartile range [IQR], 88-257) to 70 (IQR, 30-114) (p < .001) in the total population. A reduction in SOFA score was observed only in the non-CRRT groups (p < .001).
CONCLUSIONS: Intermittent meropenem bolus infusion q6h gives satisfactory TA in an ICU population with variable renal function and CRRT modality, except for ARC patients. No consistent relationship between TA and clinical endpoints were observed.
METHODS: A prospective observational study of ICU patients ≥18 years was conducted from 2014 to 2017. Patients with normal renal clearance (NRC) and augmented renal clearance (ARC) and patients on continuous renal replacement therapy (CRRT) were included. Meropenem was administered as intermittent bolus infusions, mainly at a dose of 1 g q6h. Peak, mid, and trough levels were sampled at 24, 48, and 72 h after therapy initiation. TA was defined as 100% T > 4× MIC or trough concentration above 4× MIC. Meropenem PK was estimated using traditional calculation methods and population pharmacokinetic modeling (P-metrics®). Clinical response was evaluated by change in C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, leukocyte count, and defervescence.
RESULTS: Eighty-seven patients were included, with a median Simplified Acute Physiology (SAPS) II score 37 and 90 days mortality rate of 32%. Median TA was 100% for all groups except for the ARC group with 45.5%. Median CRP fell from 175 (interquartile range [IQR], 88-257) to 70 (IQR, 30-114) (p < .001) in the total population. A reduction in SOFA score was observed only in the non-CRRT groups (p < .001).
CONCLUSIONS: Intermittent meropenem bolus infusion q6h gives satisfactory TA in an ICU population with variable renal function and CRRT modality, except for ARC patients. No consistent relationship between TA and clinical endpoints were observed.
摘要：
背景：一些研究报告，重症监护病房（ICU）患者缺乏美罗培南药代动力学/药效学（PK/PD）目标达成（TA）和间歇性推注输注治疗失败的风险。这项研究的目的是描述ICU人群中的美罗培南TA以及治疗开始后前72小时的临床反应。
方法：2014年至2017年对ICU≥18岁患者进行了前瞻性观察性研究。包括正常肾脏清除率（NRC）和增强肾脏清除率（ARC）的患者以及接受连续肾脏替代疗法（CRRT）的患者。美罗培南作为间歇性大剂量输注给药，主要剂量为1克q6h。峰,mid,和波谷水平在治疗开始后24,48和72小时采样。TA定义为100%T>4×MIC或高于4×MIC的谷浓度。使用传统计算方法和群体药代动力学建模(P-metrics®)估计美罗培南PK。通过C反应蛋白（CRP）的变化评估临床反应，序贯器官衰竭评估（SOFA）评分，白细胞计数,和退热。
结果：包括87例患者，平均简化急性生理学（SAPS）II评分37天和90天死亡率为32%。除ARC组外，所有组的TA中位数为100％，为45.5％。中位数CRP从175下降(四分位数范围[IQR]，88-257）到70（IQR，30-114）（p<.001）在总人口中。仅在非CRRT组中观察到SOFA评分降低(p<.001)。
结论：在肾功能和CRRT模式不同的ICU人群中，间歇性美罗培南推注q6h可获得令人满意的TA，除了ARC患者.在TA和临床终点之间没有观察到一致的关系。
方法：2014年至2017年对ICU≥18岁患者进行了前瞻性观察性研究。包括正常肾脏清除率（NRC）和增强肾脏清除率（ARC）的患者以及接受连续肾脏替代疗法（CRRT）的患者。美罗培南作为间歇性大剂量输注给药，主要剂量为1克q6h。峰,mid,和波谷水平在治疗开始后24,48和72小时采样。TA定义为100%T>4×MIC或高于4×MIC的谷浓度。使用传统计算方法和群体药代动力学建模(P-metrics®)估计美罗培南PK。通过C反应蛋白（CRP）的变化评估临床反应，序贯器官衰竭评估（SOFA）评分，白细胞计数,和退热。
结果：包括87例患者，平均简化急性生理学（SAPS）II评分37天和90天死亡率为32%。除ARC组外，所有组的TA中位数为100％，为45.5％。中位数CRP从175下降(四分位数范围[IQR]，88-257）到70（IQR，30-114）（p<.001）在总人口中。仅在非CRRT组中观察到SOFA评分降低(p<.001)。
结论：在肾功能和CRRT模式不同的ICU人群中，间歇性美罗培南推注q6h可获得令人满意的TA，除了ARC患者.在TA和临床终点之间没有观察到一致的关系。
