Abstract

Vancomycin (VCM) is a first-line antimicrobial agent against methicillin-resistant Staphylococcus aureus, a cause of nosocomial infections. Therapeutic drug monitoring is strongly recommended for VCM-based chemotherapy. The authors attempted to develop a simple VCM sensor based on molecularly imprinted polymer (MIP), which can be used with simple operations. Methacrylic acid (MAA), acrylamide, methylenebisacrylamide, and allylamine carboxypropionate-3-ferrocene (ACPF) were copolymerized in the presence of VCM and grafted from the surface of indium-tin oxide (ITO) to obtain MIP-coated electrodes. The MIP-grafted ITO electrode was used for differential pulse voltammetry (DPV) measurements in a buffer solution containing VCM or whole bovine blood. The obtained current depends on the VCM concentration with high linearity. The dynamic range covered the therapeutic range (20–40 μg/mL) of the VCM but was almost insensitive to teicoplanin, which has a similar structure to VCM. The ITO electrodes grafted by the same procedure except for omitting either VCM or APCF were not sensitive to VCM. The sensitivity of the MIP electrodes to VCM in whole blood and buffered saline, but the background current in blood was higher than that in saline. This high background current was also seen in the deproteinized plasma. Thus, the current is probably originated from the oxidation of low molecular weight reducing agents in the blood. The MIP-grafted ITO electrode using ACPF as a functional monomer would be a promising highly selective sensor for real-time monitoring of VCM with proper correction of the background current.

Highlights

  • Vancomycin (VCM) is the first line of an antibacterial agent against methicillinresistant Staphylococcus aureus (MRSA), a major nosocomial pathogen [1]

  • We discovered that the redox current of redox marker dissolved in the sample solution at cyclic voltammetry with molecularly imprinted polymer (MIP)-grafted indium-tin oxide (ITO) electrodes is sensitive to the concentration of the target materials used as a template

  • The ITO electrode grafted with MIP using Methacrylic acid (MAA) and allylamine carboxypropionate3-ferrocene (ACPF) is capable of molecular discrimination to distinguish VCM from teicoplanin

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Summary

Introduction

Vancomycin (VCM) is the first line of an antibacterial agent against methicillinresistant Staphylococcus aureus (MRSA), a major nosocomial pathogen [1]. Therapeutic drug monitoring (TDM) is strongly recommended for chemotherapy with VCM [1]. TDM is the individualized dosage and administration of drugs such as VCM to each patient while monitoring for factors related to therapeutic effects and side effects. Current TDM for VCM generally uses immunoassay [8,9,10], for which procedures require complicated techniques, such as pipetting, incubation, and centrifugation. There is a need for the development of sensors that can measure VCM concentrations in real-time. The purpose of this study is the development of sensors that can quickly obtain data on VCM concentrations in blood at the bedside with simple manipulation to realize the real-time monitoring of VCM in blood.

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