Reducing unnecessary antibiotic use in acute respiratory infection with host response point-of-care tests

Research question Can combined host-response point-of-care tests safely reduce unnecessary antibiotic use in adults presenting to emergency departments with acute respiratory infection? Background Antimicrobial resistance (AMR) is one of the most serious threats to human health and measures to combat it are a global priority. AMR is driven by antibiotic overuse and the commonest reason for this is acute respiratory infection (ARI). Patients with ARI are frequently treated with antibiotics, however most are caused by viruses. Previous trials of molecular point-of-care tests (POCT) detecting the viruses themselves did not show a major impact on unnecessary antibiotic use. This is likely to be because the identification of a virus does not rule out concurrent bacterial infection. New combination host-response (HR) tests aim to distinguish between viral and bacterial infections by detecting multiple immune system biomarkers and have the potential to prevent unnecessary antibiotic use by demonstrating the absence of bacterial infection. Two combination HR-POCTs have UK regulatory approval, FebriDx and MeMed BV. Although company-supported data suggests high accuracy for these tests, the strength of this evidence is considered low, and so independent studies are urgently needed. In addition, there is little published data on their impact on antibiotic use, safety or cost-effectiveness. Aims and objectives. This application describes a research programme that aims to assess the accuracy, usability, efficacy and cost-effectiveness of combined HR biomarker POCTs in safely reducing unnecessary antibiotic use, in adults with ARI. It also seeks to define a national standardised approach to the assessment of rapid combined HR tests for infection and to develop the infrastructure needed to allow high quality, rapid, multicenter evaluations of future tests. This work is strongly aligned with the aims of the NIHR, to support and prioritise AMR research, including investigating the use of diagnostics to guide antibiotics. Methods The study will be performed in three parts. 1. A fully powered diagnostic accuracy study performed on bio-banked clinical samples, using the reference standard of clinical adjudication. Measures of diagnostic accuracy will be calculated with high precision and compared between the tests. 2. A mixed-methods study evaluating measures of usability and acceptability for the two tests, including use cases, pathway mapping, and healthcare worker and patient views and experiences, using questionnaires and interviews. 3. A prospectively recruited, multicenter, randomised controlled trial (RCT) evaluating the impact of the tests on antibiotic use and clinical recovery with a health economic evaluation alongside. Anticipated impact and dissemination These studies will generate a high-certainty evidence base for the accuracy, usability, efficacy, safety and cost-effectiveness of these tests in reducing unnecessary antibiotic use in patients with ARI and may lead to NHS-wide adoption. In partnership with the Chief Scientific Officers AMR team, it will define a national standardised approach for the assessment of HR-POCTs and combined with the development of a research network, will enable rapid, gold-standard assessment of future HR-POCTs for infection. Because combined HR-POCTs can rapidly identify viral infection independently of virus type, in partnership with UKHSA, this work will inform diagnostic elements of pandemic planning.