Procalcitonin to Guide Obtaining Bloodcultures in the ICU Intensive Care Infection Score (ProBIC/ICIS)

PROBIC Rationale: Procalcitonin measurements can reduce the number of blood cultures in the ICU. Objective: The investigators suggest that PCT is a marker for blood stream infection in all patients in the ICU in whom attending physicians/ intensivists order blood culturing in the suspicion of microbial infection. The investigators want to demonstrate that its use for guiding blood culturing is cost-effective and safe compared with blood cultures alone. Study design: Prospective, non- inferiority, multicenter, single-blinded, cluster- randomised cross-over clinical trial. Intervention (if applicable): The intensive care units will be allocated into two groups: a control group (blood culture) and the intervention group (procalcitonin). Main study parameters/endpoints: Safety, expressed as mortality at day 28 and 90, with a mortality difference not exceeding a between groups difference of 10% by non-inferiority analysis. Cost-effectiveness, expressed in euro, calculated by deducting costs of procalcitonin testing from saved blood cultures compared with standard treatment spending on blood cultures in the control group. ICIS Rationale: The aim was to evaluate the Intensive Care Infection Score (ICIS) in predicting microbial infection and its sequelae in critically ill patients in whom attending physicians/ intensivists order blood culturing in the suspicion of microbial infection. Objective: Because of the complexity of the pathophysiology of systemic inflammation it is unlikely that a single parameter will have sufficient diagnostic accuracy for infection. Therefore we will study combining parameters producing a diagnostic score. Study design: Prospective, multicenter, cohort trial. Supplement for the control arm of the ProBIC study. Intervention (if applicable): Blood is drawn for daily routine laboratory measurements and collected in K3EDTA aliqnots. The ICIS score is composed of five blood-cell derived parameters which can be extracted using the same aliqnots. Main study parameters/endpoints: To develop and evaluate a blood- cell derived score to enable the diagnosis of microbial infection, its likelihood, its invasiveness and severity.

1. Safety, expressed as mortality at day 28 and 90, with a mortality difference not exceeding a between groups difference of 10% by non-inferiority analysis.

Inclusion Criteria: Patients will need to be over the age of 18 and suffering from an assumed infection deemed clinically worthy for blood culturing. Exclusion Criteria: Uncontrolled malignancy Immunosuppressive or immunostimulatory therapy Neutropenia, defined as leukocyte count less then 0.5x109/L Moribund patients Predetermined illness with an expected death within 24 hours

van der Geest PJ, Mohseni M, Nieboer D, Duran S, Groeneveld ABJ. Procalcitonin to guide taking blood cultures in the intensive care unit; a cluster-randomized controlled trial. Clin Microbiol Infect. 2017 Feb;23(2):86-91. doi: 10.1016/j.cmi.2016.10.004. Epub 2016 Oct 13.

van der Geest PJ, Mohseni M, Linssen J, Duran S, de Jonge R, Groeneveld AB. The intensive care infection score - a novel marker for the prediction of infection and its severity. Crit Care. 2016 Jul 7;20(1):180. doi: 10.1186/s13054-016-1366-6.