Title: Development of evidence based diagnostic criteria for intravascular catheter infection and an assessment of antimicrobial management of intravascular catheter infection using isothermal microcalorimetry
Funder: Health Education England

Abstract: TitleDevelopment of evidence based diagnostic criteria for intravascular catheter infection and an assessment of antimicrobial management of intravascular catheter infection using isothermal microcalorimetry. BackgroundPatients with gastrointestinal failure may require parenteral nutrition through a central intravascular catheter, but there is a risk of intravascular catheter infection. These infections have major adverse clinical effects, including patient suffering, and can be fatal. Just one of these infections costs the National Health Service GBP9900. Early detection is therefore essential so antimicrobials can be prescribed or the patient otherwise appropriately managed. However, there is currently no agreed single set of criteria for the diagnosis of infection and different sets of diagnostic criteria contradict each other and can be confusing, whilst required information may not be obtained or available. These issues can affect reported rates of infection by a difference >10% (actual) or >400% (relative). Furthermore, traditional methods to identify the most appropriate antimicrobial for an infection take time which may delay effective treatment, and there is no agreement on the choice or duration of antimicrobials that may be locked' into a catheter to effect a local action against the infection.AimsThis study has two aims: the first aim is to establish evidence based diagnostic criteria for intravascular catheter infection; and the second aim is to assess the appropriate antimicrobial management of intravascular catheter infection using isothermal microcalorimetry.Plan of investigationThe two study aims will be addressed by two work packages; WP1 and WP2.WP1 involves a prospective cohort study of 183 (up to 200) adult inpatients (18 years) prescribed parenteral nutrition. For each suspected infection, data will be obtained for various criteria that are used to diagnose infection according to different definitions. Those data include central and peripheral blood culture and culture of the tips of catheters removed for suspected infection, and clinical data such as antibiotic use and laboratory data (C-reactive protein and white cell count). Six microbiology and/or pharmacist reviewers will establish a benchmark clinical diagnosis for each suspected infection that will be used to assess the value of each potential diagnostic criterion. Infection will be defined according to different combinations of the criteria to establish the most definitive diagnosis of infection. Random elimination of data and clinical considerations will contribute to recommendations for reporting when there are missing data.WP2 involves an examination of the appropriate antimicrobial management of intravascular catheter infection using isothermal microcalorimetry to test isolates from WP1 in a category 2 microbiological laboratory. First, the potential for the microcalorimetry apparatus to detect the wild-type isolates from WP1 will be established using established methodology. Second, the potential of isothermal microcalorimetry to more rapidly identify the most appropriate antimicrobial compared to traditional methods will be assessed as up to ten microbial isolates (depending on the species identified in WP1) are tested against a battery of antimicrobials by titrating antimicrobial solutions into the isolate cultures from a reservoir. Third, the relative efficacy and ideal dwell times of a battery of antimicrobial intravascular catheter line locks' used in clinical practice will be assessed. Each lock' will be examined in an established biofilm model of S. aureus in intravascular catheters.Potential benefits to patients and the NHSMore definitive, practical and evidence based criteria to define intravascular catheter infection will improve progress towards identifying, reducing or even eliminating incidents of infection through undertaking meaningful research, audits and surveillance, and the development of nationally agreed quality indicators. In addition, improving the antimicrobial management of intravascular catheter infections through the use of academic techniques and examination of the relative efficacy and ideal dwell times of antimicrobial locks' will improve patient treatment.

Lay abstract: IntroductionPeople with a gut that functions poorly frequently develop malnutrition that can adversely affect physical and psychological well-being, health-related quality of life, and ability to work. They can receive all or part of their nutrition through a narrow tube into their vein to prevent or treat malnutrition. However, the tube can become infected and that can make patients unwell, cause distress, and in some cases patients can even die from a tube infection. Patients with infected tubes stay in hospital for longer which is unwelcome to the patients and expensive for the National Health Service. A further problem is that there is no single and simple way to determine when a tube is infected and so tube infections may not be recognised and there may be a delay in starting treatment when it is required. This project about the care of patients with tubes that may be infected will take place in a hospital and at a university.In the hospital Background There is no universally accepted definition of a tube infection and so different methods are used to identify it in different hospitals. This means patients receive different care because some patients are treated when they do not need to be and other patients that need treatment do not receive it as soon as they could. This situation is unsatisfactory for patients and also prevents consistent monitoring of high quality care. Aim The study aims to establish the correct method to determine whether or not there is an infection in a tube inserted into a vein. Plan Two hundred adult patients in hospital having nutrients into their vein through a tube will participate in this study. Every time a tube infection is suspected, information to confirm or exclude infection according to different methods will be collected whilst keeping the patients' identities confidential. No additional blood tests or invasive procedures will be carried out beyond routine care, although samples taken will undergo some additional tests. A team of experts will use the results to determine whether or not each suspected infection was a tube infection. The most appropriate information that should be collected to confirm or exclude infection can then be identified. This will help to ensure patients with a suspected tube infection have only necessary tests.At the university Background Traditional methods used to identify bacteria causing tube infections can take several days which delays treatment. A new technique that measures heat produced by bacteria will be used to identify a tube infection and the best treatment. Aim The study aims to evaluate a new technique, based on the heat produced by bacteria, to identify tube infections and the most appropriate treatment. Plan The effectiveness of different antibiotics to treat bacteria taken from patients in the hospital will be tested. This will help determine whether or not the most effective antibiotic to treat a patient could realistically be identified faster using the new method compared to traditional methods.Patient and public involvementA national patient support group and several patients in hospital helped to identify issues of importance to patients, and with the development of this plain English summary. Patients will also be involved throughout the project, including the distribution of results.Sharing the results of this workThe study findings will be presented to healthcare professionals, patients and carers. The findings will be printed in patient and professional publications and brought to the attention of policy makers to help improve guidelines, policies and procedures used for patient care in the National Health Service.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION