Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
Ther Drug Monit. 2013 Feb;35(1):63-70. doi: 10.1097/FTD.0b013e31827d496c.
Meropenem is an effective β-lactam antibiotic that is frequently used to treat serious infections in both intensive care unit (ICU) and febrile neutropenic hematology/oncology (Hem/Onc) patients. Studies suggest that to be effective, meropenem concentrations must be maintained above the inhibitory concentrations for the majority of a dosing interval. However, the pharmacokinetics (PK) of meropenem seem to differ in critically ill patients compared with healthy or less ill subjects used to select labeled dosing regimens.
This study was designed to investigate meropenem PK in critically ill patients and to see how often standard dosing regimens produced adequate plasma concentrations. A secondary objective was to investigate how achieved concentrations were related to outcomes (morbidity and mortality) in these patients.
Meropenem plasma concentrations over time were measured using a high pressure liquid chromatography assay in febrile Hem/Onc and ICU patients who were treated with standard meropenem dosing schedules. Outcomes such as fever control and survival were assessed in these patients and compared with individual meropenem PK data and with recommended target concentrations.
A total of 25 subjects including 10 febrile Hem/Onc and 15 ICU patients with a variety of serious illnesses and baseline renal function were studied. Mean peak concentrations were less variable than were pre-dose concentrations. Post peak and trough concentrations were often below recommended minimum inhibitory concentrations. Both clearance and volumes of distribution were greater than reported in less ill subjects, only in part explained by increased renal clearance. Therefore, serum concentrations often did not exceed recommended concentration targets even for moderately sensitive organisms. Inadequate concentrations were especially common in the mostly ill, febrile neutropenic Hem/Onc subjects and seemed to explain at least some therapeutic failures. Conversely, drug accumulation occurred in ICU subjects with decreased renal function.
Standard meropenem dosing regimens were inadequate in many critically ill febrile, neutropenic Hem/Onc, and septic ICU patients. These data suggest a role for meropenem concentration monitoring in such patients.
美罗培南是一种有效的β-内酰胺抗生素，常用于治疗重症监护病房（ICU）和发热性中性粒细胞减少症血液病/肿瘤学（Hem/Onc）患者的严重感染。研究表明，为了达到治疗效果，美罗培南的浓度必须在大部分给药间隔时间内保持在抑制浓度之上。然而，与用于选择标签剂量方案的健康或病情较轻的患者相比，重症患者的美罗培南药代动力学（PK）似乎有所不同。
本研究旨在研究重症患者中美罗培南的 PK，并观察标准剂量方案产生足够血浆浓度的频率。次要目的是研究这些患者中达到的浓度与结局（发病率和死亡率）的关系。
使用高效液相色谱法测定接受标准美罗培南剂量方案治疗的发热性 Hem/Onc 和 ICU 患者的美罗培南血浆浓度随时间的变化。评估这些患者的发热控制和生存等结局，并将其与个体美罗培南 PK 数据和推荐的目标浓度进行比较。
共研究了 25 名患者，包括 10 名发热性 Hem/Onc 和 15 名 ICU 患者，他们患有各种严重疾病和基线肾功能。平均峰值浓度比预剂量浓度变化小。峰后和谷浓度常低于推荐的最低抑菌浓度。清除率和分布容积均大于病情较轻患者的报道值，仅部分原因是肾清除率增加。因此，即使对于中度敏感的病原体，血清浓度也经常不超过推荐的浓度目标。在病情较重、发热性中性粒细胞减少症的 Hem/Onc 患者中，浓度不足尤其常见，这似乎至少解释了一些治疗失败的原因。相反，肾功能下降的 ICU 患者发生药物蓄积。
标准美罗培南剂量方案在许多重症发热性中性粒细胞减少症的血液病/肿瘤学患者和脓毒症 ICU 患者中并不充分。这些数据表明，在这些患者中需要进行美罗培南浓度监测。
