Development and clinical evidence generation for a rapid, cost-effective, point of care antibiotic susceptibility test for urinary tract infections

Research Question Antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi and parasites evolve and no longer respond to medicines. There were 4.95 million AMR-associated deaths in 2019 and by 2050, AMR could kill more than cancer and diabetes [1].

A key strategy to combat bacterial AMR is antibiotic susceptibility testing (AST) to identify optimum antimicrobial treatment for infections. However, current gold-standard AST takes \>2 days, relying upon overnight incubations.

Prolonged turnaround time can result in inappropriate prescription with broad-spectrum or ineffective antibiotics, risking treatment failure, prolonged hospital stays, secondary infections (e.g. C. difficile) increasing AMR rates, and a range of poor patient-related outcomes.

The proposed NIHR i4i PDA project, a collaboration between Microplate Dx, Newcastle upon Tyne Hospitals (NuTH) NHS Foundation Trust, the NIHR HealthTech Research Centre in Diagnostic and Technology Evaluation and University of Glasgow (UoG)/Digital Health Validation Lab (DHVL)/NHS Greater Glasgow & Clyde (NHSGGC) will improve AST through rapid, cost-effective, in-vitro diagnostics at the point-of-care (POC).

Background The award-winning SME Microplate Dx (MDx) has developed and validated a unique proof-of-principle AST device, with NHSGGC and NU/NuTH supporting with clinical evidence generation and care pathway analysis.

The rapid, affordable, AST platform, 'RapidPlateTM', performs AST directly from patient samples and provides personalised recommendations of appropriate antibiotics to use for bacterial or fungal infections, all <1 hour. RapidPlateTM comprises a benchtop instrument (reader) with measurement electronics, software, and readout.

Test cartridge consumables, featuring multiple hydrogel-modified electrode sensors, laden with different antibiotics to develop electrochemical growth profiles from samples, complete the novel system.

RapidPlateTM is a scalable platform technology: following first deployment to provide treatment guidance for urinary tract infections (UTIs) in a timely targeted manner, it has significant potential to scale to a range of other bacterial and fungal infections according to market need.

Aims and Objectives Following robust pre-clinical testing with NHSGGC/NuTH/NU on the proof of principle RapidPlateTM system, the aim of this project is to develop and test a beta RapidPlateTM prototype where both the reader unit and test strip architectures are representative of the final product and the system can be operated by a non-specialist, but design for manufacturing work is still necessary.

This version will be known as RapidPlate&trade;BETA. Once built, the platform will undergo a diagnostic accuracy study with Newcastle upon Tyne Hospitals Trust. Promising data collected will be put forward as part of the technical file for future regulatory submissions. Methods The i4i PDA project will significantly de-risk and advance RapidPlateTM.

Following product development of the Beta system with select partners, a diagnostic accuracy study with a leading NHS organisation (NuTH) will be performed.

Extensive regulatory activities, care pathway, health-economics and PPIE activities with multiple partners will inform and underpin technical work.

Timelines for delivery This project will be delivered via a practical 24-month project plan split into discrete interdependent work packages.

Anticipated Impact and Dissemination This proposed i4i PDA project will significantly accelerate bringing RapidPlate-UTI&trade; to market, with anticipated patient benefit within 24 months of the estimated project end (November 2026).