Title: Blood Stream Infections: Focus on Outcomes
Funder: Department of Health (England)

Abstract: Aim: To carry out a programme of linked research studies aimed at improving the management of Blood Stream Infection (BSI), and so reducing patient mortality. Background: Infection is a major concern in British hospitals: eight per cent of inpatients have infection; there are around 90-100,000 BSI per annum with a cost of £6,200 per episode in 2000, and the mortality is up to 50%. Healthcare associated research in bacterial infection in the UK is not strong, hence there is a deficiency of information on outcomes in BSI and risk factors for poor outcome. Research conducted elsewhere has been single centre and in different health systems to the NHS, hence its relevance and generalisability to the UK is limited. A number of patient factors related to underlying disease, site and severity of infection are known to impact adversely on outcome. In contrast, timely appropriate antimicrobial chemotherapy and removal of infected prosthetic materials, especially iv lines, are beneficial. Rapid laboratory based Diagnosis (RD), by speeding information flow, has had beneficial effects on antibiotic use in infected patients and may reduce mortality. As no multicentre clinical evaluations of RD have been performed in the UK, it seems the most promising area for improving management of BSI. Research plans: Based on three linked work programmes. (a) Work Package 1 (WP1): To identify modifiable risk factors for death in patients with BSI due to four key pathogens – Methicillin-resistant Staphylococcus aureus (MRSA); Pseudomonas aeruginosa; extended spectrum Blactamase (ESBL) producing E.coli/Klebsiella spp and Candida spp. Additional questions related to speed of response to therapy and length of stay will be addressed. A four centre prospective observational design will be employed. (b) Work Package 2 (WP2): To assess the impact of laboratory based rapid diagnostics on mortality in patients with BSI. Additional questions related to speed of clinical response, antibiotic use, speed of appropriate chemotherapy and length of stay will be addressed. A four centre randomised controlled trial design will be used. The RD will be provided by a molecular platform of multiplex PCR and microarray technology designed to produce high impact laboratory information within 8hrs of commencing laboratory processing of positive specimens. (c) Work Package 3: The information gained in WP1 and WP2 will feed into an educational programme using conventional and blended learning methods. We will engage with professional societies and national quality assurance schemes to inform infection practitioners about our findings. In a blended learning programme, we will use web-based learning tools such as a video-rich expert commentary on BSI, a specifically developed care bundle for BSI and a web-based forum to promote improvements in BSI management. The blended learning programme will be evaluated by telephone interviews, and at the end of the programme be made available to all infection specialists UK wide. Research Team The investigators have access through their clinical practice to a large group of patients with BSI and the relevant laboratory support to provide the molecular diagnostic platform. Specialist and reference laboratory involvement ensures expertise for indepth pathogen characterisation and antibiotic evaluation. An international panel of experts will support the team in terms of trial design, execution and analysis. Statistical and informatics experts will ensure appropriate and timely data flow and analysis. Educational expertise will be provided by links to an already funded blended learning programme for Primary Care doctors. Outputs (a) Service Outputs: Within 2-3 years, we will have identified modifiable risk factors associated with poor outcome in four key BSI. These will be included in a BSI care bundle developed for the NHS. This will be modified within 4 years in light of results from the trial of rapid diagnostics. The trial is powered to detect a reduction in BSI mortality from 15% to 12%, representing 2,500 to 3,000 saved lives per annum across the NHS. An evaluated blended educational programme on BSI will be available to the NHS as a result of WP3. The team members, as advisors to government and regulators, are well placed to use the research findings to influence policy in the NHS. (b) Research Outputs: Dissemination of results through peer-reviewed publications, regional seminars, study days and conference presentations. Hypothesis generation for future randomised controlled trials to address highlighted factors in BSI. Public Involvement: The award winning patient panel at North Bristol NHS Trust will be consulted on study design, material to be given to patients, results of the research, and dissemination strategies.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION