Delivering precision antimicrobial therapy through closed-loop control systems.

T M Rawson,A H Holmes,S Sharma,A C Gordon,A E G Cass,E De Barra,P Georgiou,D O’Hare,P Herrero,W Hope,J A Roberts,L S P Moore

doi:10.1093/jac/dkx458

Abstract

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.

Highlights

Antimicrobial resistance (AMR) threatens to be a leading cause of death by 20501 making it a global patient safety issue
In response to the observed variations in individual PK, there has been a shift in the focus of therapeutic drug monitoring (TDM) away from primarily being used to prevent toxicity caused by antimicrobials with narrow therapeutic windows, towards enhancing the efficacy of less toxic agents such as the b-lactams, in order to optimize the outcomes of treatment.[4,8,9,10,11,12,13]
Given that the free antimicrobial concentration in the interstitial fluid (ISF) is generally in equilibrium with the plasma concentration this provides an opportunity for using this technology to monitor ISF concentrations as well as estimate plasma antimicrobial concentration in near real-time without requiring plasma sampling.[36,37,38]. This may be challenging in certain situations, such as during periods of tissue hypoperfusion in critically ill patients in the intensive care unit (ICU).[39]

Summary

Introduction

Antimicrobial resistance (AMR) threatens to be a leading cause of death by 20501 making it a global patient safety issue. One potential method for avoiding these problems is the development of closed-loop systems based on minimally invasive, microneedle electrochemical sensor technology.[26] This technology has been demonstrated to be applicable to the management of other conditions, such as diabetes control through individualized insulin delivery[27,28,29,30,31] and anaesthesia control intra-operatively.[32,33] This approach offers a potential avenue for enhancing the precision of antimicrobial therapy across a number of settings where invasive monitoring techniques may not be appropriate, including the community and non-critical care hospital settings.

Results

Conclusion