Institute of Precision Medicine, Furtwangen University, Jakob-Kienzle-Strasse 17, 78054, Villingen-Schwenningen, Germany.
Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard-Karls-University Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany.
Adv Sci (Weinh). 2024 Jun;11(21):e2308806. doi: 10.1002/advs.202308806. Epub 2024 Mar 26.
One of the most important public health concerns is the increase in antibiotic-resistant pathogens and corresponding treatment of associated infections. Addressing this challenge requires more efficient use of antibiotics, achievable by the use of evidence-based, effective antibiotics identified by antibiotic susceptibility testing (AST). However, the current standard method of phenotypic AST used for this purpose requires 48 h or more from sample collection to result. Until results are available, broad-spectrum antibiotics are used to avoid delaying treatment. The turnaround time must therefore be shortened in order for the results to be available before the second administration of antibiotics. The phenotypic electrochemical AST method presented here identifies effective antibiotics within 5-10 h after sampling. Spiked serum samples, including polymicrobial samples, with clinically relevant pathogens and respective concentrations commonly found in bloodstream infections (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa) are used. Direct loading of the test with diluted serum eliminates the need for a pre-culture, as required by existing methods. Furthermore, by combining several electrochemical measurement procedures with computational analysis, allowing the method to be used both online and offline, the AST achieves a sensitivity of 94.44% and a specificity of 95.83% considering each replicate individually.
公众健康最关注的问题之一是抗生素耐药性病原体的增加以及与之相关的感染的治疗。应对这一挑战需要更有效地使用抗生素,这可以通过使用抗生素药敏试验(AST)确定的基于证据的有效抗生素来实现。然而,目前用于此目的的表型 AST 标准方法从样本采集到结果需要 48 小时或更长时间。在结果可用之前,为了避免延迟治疗,需要使用广谱抗生素。因此,必须缩短周转时间,以便在第二次使用抗生素之前获得结果。这里提出的表型电化学 AST 方法可在采样后 5-10 小时内确定有效抗生素。使用了含有临床相关病原体的加标血清样本,包括多微生物样本,以及血液感染中常见的相应浓度(大肠杆菌、金黄色葡萄球菌、肺炎克雷伯菌和铜绿假单胞菌)。与现有的方法不同,该方法直接用稀释的血清加载测试,无需进行预培养。此外,通过将几个电化学测量程序与计算分析相结合,使该方法可以在线和离线使用,该 AST 实现了 94.44%的灵敏度和 95.83%的特异性,考虑到每个重复。