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A modular β-lactamase-based thermistor biosensor platform for rapid plasma monitoring of major β-lactam antibiotic classes

Meng, Qinglai ; Wang, Youfan ; Zou, Yingying ; Zhang, Liaoyun ; Song, Dewei ; Wang, Xiedong ; Yang, Zhiqiang ; Liu, Tengfei ; Wu, Changxin and Xie, Bin LU (2027) In Talanta 312.
Abstract

Biosensors represent a promising approach for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics. However, no single biosensor strategy has yet been established to cover all four major β-lactam classes: penicillins, cephalosporins, carbapenems, and monobactams. Recently, an enzyme thermistor biosensor using New Delhi metallo-β-lactamase-1 (NDM-1) as the biorecognition element enabled the detection of penicillins, cephalosporins, and carbapenems in spiked plasma and supported accurate pharmacokinetic profiling of cefuroxime in treated patients. Here, we developed a CTX-M-14-coupled enzyme thermistor biosensor and compared its performance with that of the NDM-1 biosensor for detecting two penicillins, four extended-spectrum... (More)

Biosensors represent a promising approach for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics. However, no single biosensor strategy has yet been established to cover all four major β-lactam classes: penicillins, cephalosporins, carbapenems, and monobactams. Recently, an enzyme thermistor biosensor using New Delhi metallo-β-lactamase-1 (NDM-1) as the biorecognition element enabled the detection of penicillins, cephalosporins, and carbapenems in spiked plasma and supported accurate pharmacokinetic profiling of cefuroxime in treated patients. Here, we developed a CTX-M-14-coupled enzyme thermistor biosensor and compared its performance with that of the NDM-1 biosensor for detecting two penicillins, four extended-spectrum oxyimino-cephalosporins, one carbapenem, and one monobactam. Both β-lactamase-coupled biosensors achieved rapid response times of approximately 5 min. Across a plasma concentration range of 6.25–200 mg/L, the CTX-M-14-coupled biosensor quantified all tested penicillins, oxyimino-cephalosporins, the carbapenem, and the monobactam. In contrast, the NDM-1-coupled biosensor quantified penicillins, oxyimino-cephalosporins, and carbapenems, but not the monobactam. Although CTX-M-14 generally produced lower response signals than NDM-1 for most oxyimino-cephalosporins and the carbapenem, matrix effects for penicillins, oxyimino-cephalosporins and the monobactam were comparable between the two biosensors, with a significant difference observed only for the carbapenem. Plasma cefotaxime concentrations measured by the CTX-M-14-coupled biosensor in four treated patients closely matched UPLC–MS/MS results. Collectively, these findings support the CTX-M-14-coupled thermistor biosensor as a rapid and accurate approach for quantifying penicillins, oxyimino-cephalosporins, carbapenems, and monobactams in plasma, and highlight enzyme thermistor biosensing as a flexible platform for TDM of full-spectrum β-lactam antibiotics.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aztreonam, Biosensor, Enzyme thermistor, Pharmacokinetic analysis, Therapeutic drug monitoring, β-lactam antibiotics
in
Talanta
volume
312
article number
130306
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:42480269
  • scopus:105045024527
ISSN
1873-3573
DOI
10.1016/j.talanta.2026.130306
language
English
LU publication?
yes
id
b5896033-d11e-45d3-8f78-9a6a9d7fff7a
date added to LUP
2026-08-06 10:44:24
date last changed
2026-08-21 11:32:32
@article{b5896033-d11e-45d3-8f78-9a6a9d7fff7a,
  abstract     = {{<p>Biosensors represent a promising approach for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics. However, no single biosensor strategy has yet been established to cover all four major β-lactam classes: penicillins, cephalosporins, carbapenems, and monobactams. Recently, an enzyme thermistor biosensor using New Delhi metallo-β-lactamase-1 (NDM-1) as the biorecognition element enabled the detection of penicillins, cephalosporins, and carbapenems in spiked plasma and supported accurate pharmacokinetic profiling of cefuroxime in treated patients. Here, we developed a CTX-M-14-coupled enzyme thermistor biosensor and compared its performance with that of the NDM-1 biosensor for detecting two penicillins, four extended-spectrum oxyimino-cephalosporins, one carbapenem, and one monobactam. Both β-lactamase-coupled biosensors achieved rapid response times of approximately 5 min. Across a plasma concentration range of 6.25–200 mg/L, the CTX-M-14-coupled biosensor quantified all tested penicillins, oxyimino-cephalosporins, the carbapenem, and the monobactam. In contrast, the NDM-1-coupled biosensor quantified penicillins, oxyimino-cephalosporins, and carbapenems, but not the monobactam. Although CTX-M-14 generally produced lower response signals than NDM-1 for most oxyimino-cephalosporins and the carbapenem, matrix effects for penicillins, oxyimino-cephalosporins and the monobactam were comparable between the two biosensors, with a significant difference observed only for the carbapenem. Plasma cefotaxime concentrations measured by the CTX-M-14-coupled biosensor in four treated patients closely matched UPLC–MS/MS results. Collectively, these findings support the CTX-M-14-coupled thermistor biosensor as a rapid and accurate approach for quantifying penicillins, oxyimino-cephalosporins, carbapenems, and monobactams in plasma, and highlight enzyme thermistor biosensing as a flexible platform for TDM of full-spectrum β-lactam antibiotics.</p>}},
  author       = {{Meng, Qinglai and Wang, Youfan and Zou, Yingying and Zhang, Liaoyun and Song, Dewei and Wang, Xiedong and Yang, Zhiqiang and Liu, Tengfei and Wu, Changxin and Xie, Bin}},
  issn         = {{1873-3573}},
  keywords     = {{Aztreonam; Biosensor; Enzyme thermistor; Pharmacokinetic analysis; Therapeutic drug monitoring; β-lactam antibiotics}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Elsevier}},
  series       = {{Talanta}},
  title        = {{A modular β-lactamase-based thermistor biosensor platform for rapid plasma monitoring of major β-lactam antibiotic classes}},
  url          = {{http://dx.doi.org/10.1016/j.talanta.2026.130306}},
  doi          = {{10.1016/j.talanta.2026.130306}},
  volume       = {{312}},
  year         = {{2027}},
}