title: Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study).
abstract: Critically ill patients are at high risk of nosocomial infections, with between 20% and 40% of patients admitted to the intensive care unit (ICU) acquiring infections. These infections result in increased antibiotic use, and are associated with morbidity and mortality. Although critical illness is classically associated with hyperinflammation, the high rates of nosocomial infection argue for an importance of effect of impaired immunity. Our group recently demonstrated that a combination of 3 measures of immune cell function (namely neutrophil CD88, monocyte HLA-DR and % regulatory T cells) identified a patient population with a 2.4-5-fold greater risk for susceptibility to nosocomial infections.
  
  
  
  This is a prospective, observational study to determine whether previously identified markers of susceptibility to nosocomial infection can be validated in a multicentre population, as well as testing several novel markers which may improve the risk of nosocomial infection prediction. Blood samples from critically ill patients (those admitted to the ICU for at least 48 hours and requiring mechanical ventilation alone or support of 2 or more organ systems) are taken and undergo whole blood staining for a range of immune cell surface markers. These samples undergo analysis on a standardised flow cytometry platform. Patients are followed up to determine whether they develop nosocomial infection. Infections need to meet strict prespecified criteria based on international guidelines; where these criteria are not met, an adjudication panel of experienced intensivists is asked to rule on the presence of infection. Secondary outcomes will be death from severe infection (sepsis) and change in organ failure.
  
  
  
  Ethical approval including the involvement of adults lacking capacity has been obtained from respective English and Scottish Ethics Committees. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.
  
  
  
  NCT02186522; Pre-results.
authors.affiliation: University Division of Anaesthesia, Department of Medicine, Addenbrooke's Hospital, Cambridge, UK MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew
authors.identifier: 0000-0002-3211-3216
authors.initials: A
authors.lastname: Conway Morris
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK University of Edinburgh School of Clinical Sciences, Edinburgh Critical Care Research Group, Edinburgh, UK.
authors.forename: Deepankar
authors.identifier: 0000-0001-9971-9434
authors.initials: D
authors.lastname: Datta
authors.affiliation: Intensive Care Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Edinburgh Health Services Research Unit, Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weir
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Jillian
authors.initials: J
authors.lastname: Rennie
authors.affiliation: Edinburgh Clinical Trials Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Antonelli
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.affiliation: Becton Dickinson Bioscience, Franklin Lakes, New Jersey, USA.
authors.forename: Noel
authors.initials: N
authors.lastname: Warner
authors.affiliation: Becton Dickinson Bioscience, Franklin Lakes, New Jersey, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Keenan
authors.affiliation: Becton Dickinson Bioscience, Franklin Lakes, New Jersey, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Wang
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
authors.forename: K Alun
authors.initials: KA
authors.lastname: Brown
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
authors.forename: Sion
authors.initials: S
authors.lastname: Lewis
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
authors.forename: Tracey
authors.initials: T
authors.lastname: Mare
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
authors.affiliation: Flow Cytometry Core Facility Laboratory, Faculty of Medical Sciences, Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Hulme
authors.affiliation: Flow Cytometry Core Facility Laboratory, Faculty of Medical Sciences, Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Dimmick
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK University of Edinburgh School of Clinical Sciences, Edinburgh Critical Care Research Group, Edinburgh, UK.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D016638:Critical Illness / Q000401:mortality; D003428:Cross Infection / Q000209:etiology* / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000378:metabolism; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011446:Prospective Studies; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism; D012107:Research Design; D012121:Respiration, Artificial; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a
keywords: IMMUNOLOGY; INFECTIOUS DISEASES