Title: Bacterial impedance cytometry for rapid antibiotic susceptibility testing
Funder: Department of Health and Social Care

Abstract: The emergence and spread of antibiotic resistance is recognised as a major challenge to the current healthcare system. We have developed a novel technology which allows us to monitor the minute electrical changes which take place when bacteria are treated with an antibiotic to which they are sensitive. Supporting data has shown that this can be used with all major classes of antibiotic with Gram-negative and Gram-positive bacteria, providing signatures which are indicative of the specific mode of action of the antibiotic. This data can be used to determine if treatment with one of a range of front-line antibiotics is likely to be effective at clearing the infection and this data can be delivered to a clinician within about 30 minutes from colonies on plates or a positive blood culture. We propose to validate the technology in a laboratory environment, using a wide range of susceptible and multidrug resistant clinical isolates. This will run in parallel to the manufacture of susceptibility test cartridges and technology demonstrators which will be suitable for evaluation within a clinical microbiology department. This will allow a clinical concordance study to be performed to demonstrate the potential of the technology to direct antibiotic prescribing, looking at two major clinical indications around management of Urinary Tract Infections (UTIs) in hospitalised inpatients and treatment of bacteraemia in haematology and oncology patients. Supported by a detailed health economics assessment and active PPI, we expect to show that the technology has the potential to positively impact on patient outcomes, by improving prescription of effective antibiotics and financial benefits linked to de-escalation of costly therapy, early discharge from high dependency hospital wards to the community and by reducing isolation time for patients with high-risk bacterial isolates. All of this work contributes to improved antibiotic stewardship with benefits to the broader community.

Lay abstract: What is the problem we are addressing? The emergence of bacteria which are highly resistant to treatment with antibiotics has raised significant concerns with doctors and patients in and out of hospital and is considered as a major public health problem. One way to try and improve things is to develop tests which will show which antibiotic will treat which infection in particular patients. This will improve patient care and reduce the use of antibiotics, which has contributed to the emergence of resistance problems, so hopefully we will see less resistance in future. It will also build confidence in patients/carers that they are getting the right treatment at the right time. The current methods for determining which antibiotic will work for which bacterial infection can take anything between 24 and 72 hour and is dependent on the speed of growth of the bacteria. This delay is a problem for patients and for doctors waiting to find out which is the most appropriate treatment and can lead to the incorrect antibiotic given in the first instance. How will we address the problem? The technology to be utilised in the current study will enable the rapid determination of susceptibility of bacteria to different types of antibiotic, with the potential to deliver a complete answer to clinicians within 1-2 hours. This will enable doctors to make decisions about which antibiotic to use or to switch to, maximising the chances of the treatment being effective. The proposed study will build a prototype suitable for use within a busy diagnostic laboratory, robustly demonstrating that it works with a large number of different types of bacteria. The data will be compared with the current gold standard tests to provide proof that the results are better than the current tests or that they are as good but capable of delivering answers to the doctors much quicker, enabling them to change treatment. The involvement of patients and the public in this study Given the importance of tackling antimicrobial resistance (AMR) to the general public, the project team will involve a range of people to discuss how the technology will be used, including doctors, scientists, hospital managers and most importantly patients and their families, carers and the public. A recent workshop with patients and the public (held by the James Lind Alliance on the topic of Healthcare Associated Infections (HCAI)) highlighted the importance the public place on getting such tests into the NHS and hence our study is a key patient/public priority. The recent evaluation of the implementation of the UK Government s AMR strategy again showed the importance patients/carers placed on having rapid diagnostic tests to improve and speed up treatment.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE