1. Academic Validation
  2. The New Delhi metallo-β-lactamase-1 biosensor rapidly and accurately detected antibiotic plasma concentrations in cefuroxime-treated patients

The New Delhi metallo-β-lactamase-1 biosensor rapidly and accurately detected antibiotic plasma concentrations in cefuroxime-treated patients

  • Int J Antimicrob Agents. 2024 May 31;64(2):107229. doi: 10.1016/j.ijantimicag.2024.107229.
Qinglai Meng 1 Yao Wang 2 Yali Long 3 Qi Wang 4 Yajing Gao 2 Junsheng Tian 4 Changxin Wu 5 Bin Xie 6
Affiliations

Affiliations

  • 1 Institute of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, Taiyuan, China. Electronic address: qmeng@sxu.edu.cn.
  • 2 Institute of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, Taiyuan, China.
  • 3 Hospital of Shanxi University, Shanxi University, Taiyuan, China.
  • 4 Modern Research Center for Traditional Chinese Medicine, Shanxi University and Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Shanxi University, Taiyuan, China.
  • 5 Institute of Biomedical Sciences, The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, Taiyuan, China. Electronic address: cxw20@sxu.edu.cn.
  • 6 Pure and Applied Biochemistry, Department of Chemistry, Lund University, Lund, Sweden. Electronic address: bin.xie@tbiokem.lth.se.
Abstract

Objectives: Therapeutic drug monitoring (TDM) of β-lactam Antibiotics in critically ill patients may benefit dose optimisation, thus improving therapeutic outcomes. However, rapidly and accurately detecting these Antibiotics in blood remains a challenge. This research group recently developed a thermometric biosensor called the New Delhi metallo-β-lactamase-1 (NDM-1) biosensor, which detects multiple classes of β-lactam Antibiotics in spiked plasma samples.

Methods: This study assessed the NDM-1 biosensor's effectiveness in detecting plasma concentrations of β-lactam Antibiotics in treated patients. Seven patients receiving cefuroxime were studied. Plasma samples collected pre- and post-antibiotic treatment were analysed using the NDM-1 biosensor and compared with liquid chromatography coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results: The biosensor detected plasma samples without dilution, and a brief pre-treatment using a polyvinylidene fluoride filter significantly lowered matrix effects, reducing the running time to 5-8 minutes per sample. The assay's linear range for cefuroxime (6.25-200 mg/L) covered target concentrations during the trough phase of pharmacokinetics in critically ill patients. The pharmacokinetic properties of cefuroxime in treated patients determined by the NDM-1 biosensor and the UPLC-MS/MS were comparable, and the cefuroxime plasma concentrations measured by the two methods showed statistically good consistency.

Conclusion: These data demonstrate that the NDM-1 biosensor assay is a fast, sensitive, and accurate method for detecting cefuroxime plasma concentrations in treated patients and highlights the NDM-1 biosensor as a promising tool for on-site TDM of β-lactam Antibiotics in critically ill patients.

Keywords

Antimicrobial resistance; Beta-lactam antibiotics; Critically ill patients; Pharmacokinetics; Therapeutic drug monitoring; Thermometric biosensor.

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