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β-内酰胺类抗生素个体化治疗的临床现场监测。

Clinical on-site monitoring of ß-lactam antibiotics for a personalized antibiotherapy.

机构信息

Department of Microsystems Engineering, University of Freiburg, 79110, Freiburg, Germany.

Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany.

出版信息

Sci Rep. 2017 Jun 9;7(1):3127. doi: 10.1038/s41598-017-03338-z.

DOI:10.1038/s41598-017-03338-z
PMID:28600499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5466632/
Abstract

An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients' outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml) from only 1 µl of serum. The system's applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

摘要

适当的抗生素治疗对于患者的安全和康复至关重要。根据患者的临床状况,有效消除感染所需的剂量可能会有所不同。剂量不足不仅会降低抗生素的疗效,还会促进抗菌药物耐药性的出现。因此,个性化治疗对于改善患者的预后非常重要,并将长期减少多药耐药性的流行。在这种情况下,现场监测抗生素的血药浓度对于促进抗生素治疗的个体化调整至关重要。在这里,我们提出了一种仿生方法,用于床边监测未处理血浆样本中游离可及的β-内酰胺抗生素,包括青霉素(哌拉西林)和头孢菌素(头孢呋辛和头孢唑林)。该系统将一次性微流控芯片与天然存在的青霉素结合蛋白相结合,形成了一种高性能平台,能够从仅 1 µl 的血清中测量非常低的抗生素浓度(低于 6ng/ml)。该系统通过监测接受β-内酰胺类抗生素治疗的手术患者的药代动力学,成功证明了其在个性化抗生素治疗中的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/b792bc625372/41598_2017_3338_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/e38567304191/41598_2017_3338_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/40122d6d3050/41598_2017_3338_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/5806b9a4398a/41598_2017_3338_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/5e1fecf9ff71/41598_2017_3338_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/b792bc625372/41598_2017_3338_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/e38567304191/41598_2017_3338_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/40122d6d3050/41598_2017_3338_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/5806b9a4398a/41598_2017_3338_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/5e1fecf9ff71/41598_2017_3338_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4b/5466632/b792bc625372/41598_2017_3338_Fig5_HTML.jpg

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