Title: Point-of-care antibiotic susceptibility testing to aid urinary tract infection treatment using dip-and test microcapillary devices
Funder: Department of Health and Social Care

Abstract: A high prevalence of urinary tract infection (UTI), increase in antibiotic resistance and slow turnaround of current tests drive an unmet need for accurate antibiotic susceptibility testing (AST) for use in near-patient settings. Current methods take more than 24h to get results, require bulky laboratory equipment and a skilled workforce. This research project aligns with NHS priorities and the UK s 20-year vision and 5-year national action plan on AMR. Trimethoprim, used first line for UTI, can no longer be used routinely as resistance rates are reaching 30%. Our solution is to miniaturise AST performed by microbiology laboratories, inside inexpensive microcapillary film strips allowing AST to be easily performed at Point-of-Care (POC), reducing time to diagnosis, and supporting antibiotic selection. The overall aim of this research is to develop our proof-of-concept microcapillary system into a POC AST device for patients with suspected UTI to a point where it can be submitted for regulatory approval and adopted. We will design, develop, and build a prototype of the POC device, test the device usability, clinically validate the device, and generate evidence of health economic and patient benefits. During two clinical studies, samples will be collected from patients presenting to the emergency department with UTI symptoms. This will generate pivotal performance data to firstly finalise the POC system (Yr1,2), and secondly evaluate POC system performance in a leading NHS hospital (Yr3) against clinical reference standard microbiology tests. In parallel, detailed user requirements will be defined through stakeholder engagement. Oxford AHSN will conduct a health economic evaluation and lead on engagement with patients and public. Budget has been allocated for regulatory advice to support commercialisation planning. The key output of this research will be a rapid, accurate POC diagnostic technology ready for regulatory approval that has the potential to be a game-changer in the field of AST. Primary research findings will be published in peer-reviewed journals regarding device optimisation and testing with clinical samples on the bench and in a hospital setting. A valuable dataset will be generated which may lead to additional health data opportunities. We will engage with the scientific, clinical NHS and wider healthcare / AMR communities, patients, and the public. The results of the research will be promoted to the clinical and laboratory audiences through presentations at conferences. Resistant strains of infection are associated with longer illness duration, increased re-consultation, and increased overall healthcare costs and NHS workloads. This research will result in better patient outcomes through informed selection of antibiotics and reduced AMR levels through better use of antibiotics. In the current standard of care, it takes between 24 and 72 hours to obtain results for antibiotic susceptibility analysis, our research will reduce this to between 4 to 6 hours. Currently only urine dipstick tests are used in primary care as an indication of the presence of infection which have sensitivity as low as 45%, this research will make accurate POC AST available for the first time in a near patient and primary care setting.

Lay abstract: &ldquo;Water infections&rdquo; or Urinary Tract Infections (UTI) are a very common condition. UTI accounts for up to 3% of all General Practice (GP) appointments and 15% of all antibiotics prescribed within general practice. UTI is the most common infection in women, up to 10% of women in the UK every year suffer from a UTI. UTI may also develop into sepsis, an unusually severe response to an infection. UTI is also a significant cause of death accounting for 4835 deaths in England and Wales in 2012. In England, NHS hospitals spend &pound;400 million per year treating UTI. Currently urine dipstick tests are used in general practice to indicate a UTI. Although dipstick tests give instant results, they are known to be unreliable. Based on clinical diagnosis in conjunction with the result of the urine dipstick test, doctors usually prescribe a broad-spectrum antibiotic (one that is effective against many types of bacteria). For 34-60% of people diagnosed with UTI, antibiotics are prescribed before their diagnosis can be confirmed by the laboratory. Ideally, the identity of the bacteria and its susceptibility to specific antibiotics is known before antibiotic treatment, giving the patient treatment targeted to the type of infection they have. To identify the specific bacteria causing the infection, a urine specimen is sent to a laboratory where it is grown and tested to determine which antibiotic would be most effective against it. It takes 1-3 days to obtain results, and samples aren t taken from all patients. This overuse of broad-spectrum antibiotics has led to the emergence of bacteria which are resistant to several antibiotics and can also put patients at risk of infection from &ldquo;super bacteria&rdquo;. Antibiotic resistant infection is associated with longer recovery times, increased GP visits and increased overall healthcare costs. This project will develop and evaluate a rapid, portable test that checks for antibiotic resistance in bacteria responsible for UTIs so that doctors can treat the infection with the most appropriate antibiotic, maximising the likelihood that the infection will be cleared. So far, we have shown our new technology works well as a proof of concept. We have interviewed both patients and clinicians who are highly supportive of this project. This research will fully develop a product ready for regulatory approval and NHS use by: 1. undertaking a clinical study to define the fastest, most accurate test with real patient samples 2. designing a final prototype device that meets regulatory standards 3. testing the device in a leading hospital 4. analysing the health economic and patient benefits 5. working with clinicians, patients and public to establish how to adopt this product into the NHS 6. sharing the project progress with clinicians, industry, patients and the public

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION