SIRS and Bacterial Sepsis Discrimination by Biomarkers in ICU
SIRS and Bacterial Sepsis Discrimination by Biomarkers in ICU
Aim of the study : The primary aim of the investigators study is to highlight the presence of
 biomarkers (biological indicators of the presence of inflammation or infection) of infectious
 processes during the systemic inflammatory response (SIRS) allowing, first to discriminate
 non-infectious inflammation from infectious processes and secondary to determine the
 microbial pathogen responsive of the infection. For this purpose the investigators will
 conduct a combinatorial approach of several blood markers including usual markers of
 inflammation and other blood and cells markers. Expression of small pieces of RNA (miRNA)
 known to inhibit determined gene expression, will also be analysed in monocytes (a specific
 group of white blood cells involved in the fist line of defences against microbes.

 Study design : For this purpose the investigators will include 300 patients admitted to the
 intensive care unit with suspicion of infection. Serial blood sample will be take for
 biological parameters analysis. Efficiency of each single parameters and of different
 combinations of different markers to determine the presence or absence of infection
 responsive of clinical inflammation will be studied.
Aim of the study : The project's main objective is the establishment of the diagnostic
 performance of the association of diagnostic markers of infectious processes linked to the
 pathogen or host during the systemic inflammatory response syndromes (SIRS) in critical care
 patients allowing, first to discriminate non infectious SIRS from sepsis and, secondary to
 determine the microbial pathogen responsive of the inflammation. For this purpose, we will
 conduct a combinatorial approach of several plasma markers including usual markers (CRP, PCT,
 other soluble mediators (soluble TREM-1, IL-6, IL-1Ra, IL-10, CXCL2, CXCL8, CCL2 and CCL5),
 cell markers (CD14 / HLA-DR expression on monocytes and TLR2, 4, 9 expression on NK cells)
 together with modified expression of microRNA (miRNA) in circulating monocytes.

 Study design : This study will include patients admitted to the ICU with SIRS and suspected
 sepsis, according to usual criteria. Infection definition will be based on a combination
 clinical, bacteriological and cyto-or histo-pathological according to the disease involved.

 A serial measurement of biological parameters previously described will be realized from D0
 to D3.

 Evaluation criteria : The primary endpoint is to determine the ability of each individual
 parameter and of the different combination to discriminate between sepsis and noninfectious
 inflammation. The diagnostic performance of biomarkers studied will be done by calculating
 the sensitivity, specificity, positive and negative predictive value of each test alone or in
 combination with respect to the existence of an infection (sepsis) or not (SIRS). According
 to data from the literature and our own experience, the expected proportion of patients with
 sepsis among the holders of SIRS was 50%. The discriminatory ability of each test will be
 performed by using ROC curves and calibration using the Hosmer-Lemeshow several layers of
 increasing severity. The level of service provided is a p-value <5%. There are no plans to
 statistical criteria for stopping the search in case of biological data missing.

 The value of the area under the ROC curve (AUC) of the PCT is 78% (95% CI 69-77). Assuming
 that one of the tests or combinatorial approach will increase the AUC to 85%, the number of
 patients needed for this study is estimated to be 300.

 Conduct of research : Study will be conducted in 5 different sites. Patients admitted with or
 who develop a SIRS during hospitalization will be included. There will be nothing peculiar in
 the therapeutic management and patients will be covert by the international guidelines.

 -  Inclusion criteria:

 -  Patient admitted with or who develop SIRS during ICU hospitalisation

 -  Two or more parameter of the SIRS definition

 -  Patient does not preclude its participation in the study

 -  Non inclusion criteria

 -  Decision of withdrawal or withholding therapeutic interventions

 -  No affiliation to a social security scheme

 The measurement of biological endpoints will be conducted once daily, from D0 (admission) to
 D2 using a blood sample. The study of monocyte expression of miRNA will be performed on a
 portion of the cohort, corresponding to patients selected on the St. Joseph site (intensive
 care unit and surgical intensive care unit) because of complexity to implement, and cost
 level (requiring specific funding).

 Total projected duration of the search: The recruitment period will run for 23 months with
 the aim to include all 300 patients. Patients included in the research will be followed until
 day 28 or day of hospital leaving, if earlier.

 Stopping rules of the study to a patient: patient can discontinue their participation at any
 time during the research.

 Security evaluation : Being a non-interventional study (biological collection) in the usual
 care of patients, no serious adverse event is expected to be related to research.

 Any new data security, potentially leading to a reassessment of the benefits and risks of
 research, or which may be sufficient to consider changes in the conduct of research must be
 reported.
Inclusion Criteria:

 -  Age> = 18 years

 -  Patient hospitalized in ICU with a diagnosis of SIRS:

 -  Temperatures above 38 ° C or below 36 ° C

 At least one other criterion from:

 -  Heart rate> 90 bpm

 -  Respiratory rate above 20 breaths / min or PaCO2 <32 mmHg

 -  Leukocytosis greater than or less than 4000/mm3 12000/m3

 -  Patient admitted in intensive care for less than 12 hours

 -  Patient does not preclude its participation in the study.

 Exclusion Criteria:

 -  Decision to limit treatment before potential inclusion in the study

 -  No affiliation to a social security scheme (beneficiary or assignee)