Xiaoyong Xu, Jinglin Wang, Guangfei Wang, Huimin Zhang, Hong Xu, Zhiping Li
Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pediatr. 2023 Jan 10;10:1055200. doi: 10.3389/fped.2022.1055200. eCollection 2022.
Therapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid.
Paired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots.
The microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well ( > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively.
This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.
治疗药物监测（TDM）已被证明对重症患者具有临床益处。然而，这对循环血容量小的新生儿或儿童来说是一项负担。在此，我们旨在开发并验证一种微量采样TDM平台（包括干血斑（DBS）和毛细血管微量样本（CMS）），用于同时定量测定万古霉素、美罗培南和利奈唑胺。
从重症监护病房（ICU）获取配对的DBS和CMS样本，以评估其临床应用。根据DBS浓度计算估计血浆浓度（EPC）。使用Deming回归和Bland-Altman差异图评估方法之间的一致性。
微量采样方法验证显示出优异的可靠性，并且与所研究人群的样本基质和血细胞比容范围的分析具有良好的兼容性。DBS和CMS的准确度和精密度结果均在可接受范围内，样本在室温下分别稳定至少2天和8小时。血细胞比容对CMS无影响，但对DBS测量有轻微影响。CMS和DBS的抗生素浓度相关性良好（>0.98）。DBS样本与CMS样本中的药物浓度比，万古霉素为1.39，美罗培南为1.34，利奈唑胺为0.94。使用个体血细胞比容范围从DBS计算得出的EPC，万古霉素（斜率：1.06）和美罗培南（斜率：1.04）呈现出可比的绝对值，分别为所测CMS浓度的98%和99%。
本研究提供了一个经临床验证的微量采样TDM平台，可快速定量三种抗生素，适用于在重症儿童中进行实时TDM指导的抗菌治疗个体化。
