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抗黏菌素、万古霉素、达托霉素和美罗培南抗体的开发及酶联免疫吸附测定表征:一种治疗药物监测方法

Development and ELISA Characterization of Antibodies against the Colistin, Vancomycin, Daptomycin, and Meropenem: A Therapeutic Drug Monitoring Approach.

作者信息

Garzon Vivian, Salvador J-Pablo, Marco M-Pilar, G-Pinacho Daniel, Bustos Rosa-Helena

机构信息

Doctoral Programme of Biosciences, Universidad de La Sabana, Chía 140013, Colombia.

Therapeutic Evidence Group, Clinical Pharmacology, Universidad de La Sabana, Chía 140013, Colombia.

出版信息

Antibiotics (Basel). 2024 Jun 27;13(7):600. doi: 10.3390/antibiotics13070600.

Abstract

More than 70% of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of "last-line" antimicrobial therapies for the treatment of multi-resistant bacteria. These antibiotics include Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin), and Carbapenem (Meropenem). However, due to the toxicity of these types of molecules, it is necessary to develop new rapid methodologies to be used in Therapeutic Drug Monitoring (TDM). TDM could improve patient outcomes and reduce healthcare costs by enabling a favorable clinical outcome. In this way, personalized antibiotic therapy emerges as a viable option, offering optimal dosing for each patient according to pharmacokinetic (PK) and pharmacodynamic (PD) parameters. Various techniques are used for this monitoring, including high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and immunoassays. The objective of this study is the development and characterization by ELISA of specific polyclonal antibodies for the recognition of the antibiotics Vancomycin (glycopeptide), Colistin (polymyxin), Daptomycin (lipopeptide), and Meropenem (carbapenem) for future applications in the monitoring of these antibiotics in different fluids, such as human plasma. The developed antibodies are capable of recognizing the antibiotic molecules with good detectability, showing an IC50 of 0.05 nM for Vancomycin, 7.56 nM for Colistin, 183.6 nM for Meropenem, and 13.82 nM for Daptomycin. These antibodies offer a promising tool for the precise and effective therapeutic monitoring of these critical antibiotics, potentially enhancing treatment efficacy and patient safety.

摘要

超过70%的细菌对所有或几乎所有已知抗菌药物耐药,这就需要开发新型抗菌药物或使用“最后一线”抗菌疗法来治疗多重耐药细菌。这些抗生素包括糖肽类(万古霉素)、多粘菌素类(黏菌素)、脂肽类(达托霉素)和碳青霉烯类(美罗培南)。然而,由于这类分子具有毒性,有必要开发新的快速方法用于治疗药物监测(TDM)。TDM通过实现良好的临床疗效,可改善患者预后并降低医疗成本。这样一来,个性化抗生素治疗成为一种可行的选择,可根据药代动力学(PK)和药效学(PD)参数为每位患者提供最佳剂量。为此监测使用了各种技术,包括高效液相色谱法(HPLC)、气相色谱 - 质谱联用(GC - MS)和免疫测定法。本研究的目的是通过酶联免疫吸附测定(ELISA)开发和鉴定特异性多克隆抗体,用于识别抗生素万古霉素(糖肽类)、黏菌素(多粘菌素类)、达托霉素(脂肽类)和美罗培南(碳青霉烯类),以便未来用于监测不同体液(如人血浆)中的这些抗生素。所开发的抗体能够以良好的可检测性识别抗生素分子,万古霉素的半数抑制浓度(IC50)为0.05 nM,黏菌素为7.56 nM,美罗培南为183.6 nM,达托霉素为13.82 nM。这些抗体为精确有效地治疗监测这些关键抗生素提供了一种有前景的工具,可能提高治疗效果和患者安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4924/11273741/582c5985265f/antibiotics-13-00600-g001.jpg

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