Biosensors for antimicrobial optimisation

Abstract

1.3 million people a year die from antimicrobial resistant (AMR) infections, and without improved stewardship of antimicrobials to reduce further development of AMR, the number of deaths from AMR infections is likely to rise to 10 million deaths a year by 2050. One contributing factor to the development of AMR is suboptimal dosing of antimicrobials. Therapeutic drug monitoring offers a potential route to optimising dosing, however current techniques generally rely on mass spectrometry which is prohibitively expensive and time consuming to implement widely and is often unavailable in low resource settings. Therapeutic drug monitoring is therefore rarely used for antimicrobials. Biosensors offer a solution to this problem, providing inexpensive fast methods for monitoring antimicrobial concentrations for optimisation of antimicrobial dosing. This thesis discusses three biosensor technologies. Firstly, developing a point of care disposable electrochemical biosensor for the detection of Cefiderocol and then expanding this technology into a continuous microneedle sensor. Secondly developing a detailed model of enzymatic biosensor and applying it to assessing the viability of beta lactamase sensors for monitoring beta lactams. Lastly, producing a new method for the chronoamperometric interrogation of aptamer sensors, with the aim of removing the need for individual calibration of aptamer sensors.