The NDM-1 biosensor rapidly and accurately detected antibiotic plasma concentrations in Cefuroxime-treated patients

Therapeutic drug monitoring (TDM) of β-lactam antibiotics in critically ill patients may benefit dose optimization, thus improving therapeutic outcomes. However, rapidly and accurately detecting these antibiotics in blood remains a challenge. Our research group recently developed a thermometric biosensor called the New Delhi metallo-β-lactamase-1 (NDM-1) biosensor, which detected multiple classes of β-lactam antibiotics in spiked plasma samples. This study assesses the NDM-1 biosensor's effectiveness in detecting plasma concentrations of β-lactam antibiotic in treated patients. Seven patients receiving Cefuroxime were studied. Plasma samples collected pre- and post-antibiotic treatment were analyzed using the NDM-1 biosensor and compared with liquid chromatography coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The biosensor detected plasma samples without dilution, and a brief pre-treatment using a PVDF filter significantly lowered matrix effects, reducing the running time to 5-8 minutes per sample. The assay's linear range for Cefuroxime (6.25 to 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 a statistically good consistency. These data demonstrate that the NDM-1 biosensor assay is a fast, sensitive, and accurate method for detecting Cefuroximeplasma concentration 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.