Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay
| Autor: | Michael Mecklenburg, Yujia Fu, Dewei Song, Jianyi Liu, Changxin Wu, Aiping Yue, Xiangyu Yao, Yali Long, Qinglai Meng, Bin Xie, Yao Wang, Shuaiyan Tian |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.drug_class Avibactam therapeutic drug monitoring Cephalosporin Antibiotics critically ill patients RM1-950 Pharmacology NDM-1 Biochemistry Microbiology Meropenem Article chemistry.chemical_compound β-lactam antibiotics medicine polycyclic compounds Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Monobactams Vaborbactam medicine.diagnostic_test thermometric biosensor Penicillin Infectious Diseases chemistry Therapeutic drug monitoring Therapeutics. Pharmacology medicine.drug |
| Zdroj: | Antibiotics Volume 10 Issue 9 Antibiotics, Vol 10, Iss 1110, p 1110 (2021) |
| ISSN: | 2079-6382 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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