Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.
Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.
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基于适体的血清万古霉素监测相对于自动免疫测定的分析验证。
DOI：
10.1021/acssensors.3c01868
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发表时间：
2024
期刊：
影响因子：
8.9
通讯作者：
Arroyo-Currás,Netzahualcóyotl
中科院分区：
文献类型：
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作者：
Liu,Yu;Mack,JohnO;Shojaee,Maryam;Shaver,Alexander;George,Ankitha;Clarke,William;Patel,Neel;Arroyo-Currás,Netzahualcóyotl
监测患者生物液中的治疗药物浓度的做法可以显著改善临床结果，同时将不良副作用降至最低。这种做法的一个典型例子是重症监护病房中的万古霉素剂量。如果剂量正确，万古霉素可以有效治疗耐甲氧西林金黄色链球菌(MRSA)感染。然而，如果剂量太高或太低，它也会导致肾毒性或无法杀灭细菌。尽管不可否认，治疗药物监测对实现有效性很重要，但在实践中仍然不方便，主要是因为样品收集、运送到中央设施和使用昂贵仪器进行分析的过程漫长。此外，集中式临床实验室还可能出现积压，这并不少见，可能会导致生物液采样和浓度测量之间的额外延迟，从而对临床结果产生负面影响。在这里，我们探索使用基于护理点的电化学适配子(E-AB)传感器的可能性，以最大限度地减少生物液采样和药物测量之间的时间延迟。具体地说，我们进行了一项临床一致性研究，将E-AB传感器的测量结果与基准自动竞争免疫分析法进行比较，以监测血清中的万古霉素。我们的结果表明，E-ABS对药物的活性形式游离万古霉素─的选择性高于对总万古霉素的选择性。相比之下，竞争性免疫分析法测量万古霉素总量，包括蛋白质结合药物和游离药物。在一项由85个临床样本组成的初步研究中，考虑到这些差异，我们证明E-AB万古霉素测定与基准免疫分析方法获得了95%的正相关性。因此，我们得出结论，E-AB传感器可以在低谷抽样时提供临床上有用的患者样本分层，以指导有效的万古霉素剂量推荐。
The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. A model example of this practice is vancomycin dosing in intensive care units. If dosed correctly, vancomycin can effectively treat methicillin-resistant streptococcus aureus (MRSA) infections. However, it can also induce nephrotoxicity or fail to kill the bacteria if dosed too high or too low, respectively. Although undeniably important to achieve effectiveness, therapeutic drug monitoring remains inconvenient in practice due primarily to the lengthy process of sample collection, transport to a centralized facility, and analysis using costly instrumentation. Adding to this workflow is the possibility of backlogs at centralized clinical laboratories, which is not uncommon and may result in additional delays between biofluid sampling and concentration measurement, which can negatively affect clinical outcomes. Here, we explore the possibility of using point-of-care electrochemical aptamer-based (E-AB) sensors to minimize the time delay between biofluid sampling and drug measurement. Specifically, we conducted a clinical agreement study comparing the measurement outcomes of E-AB sensors to the benchmark automated competitive immunoassays for vancomycin monitoring in serum. Our results demonstrate that E-ABs are selective for free vancomycin─the active form of the drug, over total vancomycin. In contrast, competitive immunoassays measure total vancomycin, including both protein-bound and free drug. Accounting for these differences in a pilot study consisting of 85 clinical samples, we demonstrate that the E-AB vancomycin measurement achieved a 95% positive correlation rate with the benchmark immunoassays. Therefore, we conclude that E-AB sensors could provide clinically useful stratification of patient samples at trough sampling to guide effective vancomycin dose recommendations.