• Conway Morris Andrew A 0000-0002-3211-3216 University Division of Anaesthesia, Department of Medicine, Addenbrooke's Hospital, Cambridge, UK MRC Centr, Deepankar Datta, Manu Shankar-Hari, Christopher J Weir, Jillian Rennie, Jean Antonelli, Adriano G Rossi, Noel Warner, Jim Keenan, Alice Wang, K Alun Brown, Sion Lewis, Tracey Mare, A John Simpson, Gillian Hulme, Ian Dimmick, and Timothy S Walsh.
• University Division of Anaesthesia, Department of Medicine, Addenbrooke's Hospital, Cambridge, UK MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
• BMJ Open. 2016 Jul 18; 6 (7): e011326.

IntroductionCritically 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.Methods And AnalysisThis 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.Ethics And DisseminationEthical 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.Trial Registration NumberNCT02186522; Pre-results.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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