Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay
Qinglai Meng,
Yao Wang,
Yali Long,
Aiping Yue,
Michael Mecklenburg,
Shuaiyan Tian,
Yujia Fu,
Xiangyu Yao,
Jianyi Liu,
Dewei Song,
Changxin Wu,
Bin Xie
Affiliations
Qinglai Meng
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Yao Wang
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Yali Long
Hospital of Shanxi University, Shanxi University, Taiyuan 030006, China
Aiping Yue
Hospital of Shanxi University, Shanxi University, Taiyuan 030006, China
Michael Mecklenburg
Omik Bioscience AB, SE-22363 Lund, Sweden
Shuaiyan Tian
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Yujia Fu
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Xiangyu Yao
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Jianyi Liu
Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing 100029, China
Dewei Song
Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing 100029, China
Changxin Wu
The Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Institute of Biomedical Sciences, Shanxi University, Taiyuan 030006, China
Bin Xie
Pure and Applied Biochemistry, Department of Chemistry, Lund University, SE-22100 Lund, Sweden
Currently, assays for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of β-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-β-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of β-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of β-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the β-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound β-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total β-lactam antibiotics present in the blood of critically ill patients.
