万古霉素
适体
体内
药代动力学
化学
生物医学工程
材料科学
生物物理学
药理学
医学
生物
分子生物学
金黄色葡萄球菌
生物技术
细菌
遗传学
作者
Alexander Shaver,J. D. Mahlum,Karen Scida,Melanie L. Johnston,Miguel Aller Pellitero,Yao Wu,Gregory V. Carr,Netzahualcóyotl Arroyo‐Currás
出处
期刊:ACS Sensors
[American Chemical Society]
日期:2022-11-23
卷期号:7 (12): 3895-3905
被引量:12
标识
DOI:10.1021/acssensors.2c01910
摘要
The measurement of serum vancomycin levels at the clinic is critical to optimizing dosing given the narrow therapeutic window of this antibiotic. Current approaches to quantitate serum vancomycin levels are based on immunoassays, which are multistep methods requiring extensive processing of patient samples. As an alternative, vancomycin-binding electrochemical, aptamer-based sensors (E-ABs) were developed to simplify the workflow of vancomycin monitoring. E-ABs enable the instantaneous measurement of serum vancomycin concentrations without the need for sample dilution or other processing steps. However, the originally reported vancomycin-binding E-ABs had a dissociation constant of 45 μM, which is approximately 1 order of magnitude higher than the recommended trough concentrations of vancomycin measured in patients. This limited sensitivity hinders the ability of E-ABs to accurately support vancomycin monitoring. To overcome this problem, here we sought to optimize the length of the vancomycin-binding aptamer sequence to enable a broader dynamic range in the E-AB platform. Our results demonstrate, via isothermal calorimetry and E-AB calibrations in undiluted serum, that superior affinity and near-equal sensor gain in vitro can be achieved using a one-base-pair-longer aptamer than the truncated sequence originally reported. We validate the impact of the improved binding affinity in vivo by monitoring vancomycin levels in the brain cortex of live mice following intravenous administration. While the original sequence fails to resolve vancomycin concentrations from baseline noise (SNR = 1.03), our newly reported sequence provides an SNR of 1.62 at the same dose.
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