Mediastinitis and Staphylococcus Aureus

Study Overview
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Brief Summary
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Cardiac surgery with extracorporeal circulation (ECC) yields a deep immune system dysfunction that exposes patients to postoperative infectious complications. Among these, post-operative mediastinitis with Staphylococcus aureus (SA) generates significant morbidity and mortality. Two radically different approaches have been proposed in recent years to reduce the incidence of this complication. A first approach has attempted, without real success, to decrease postoperative immunosuppression. The second, more efficient, consisted of screening and preoperatively treating patients colonized with SA. However, although its incidence has decreased, postoperative mediastinitis remains a terrible nosocomial infection. The authors believe that a thorough analysis of the immunological changes induced by cardiac surgery will initiate active therapeutics to reduce the post-operative immunosuppression phase, thereby decreasing the risk of nosocomial infections. In addition, a study of the interactions between the operated (host) and staphylococcus aureus (pathogenic) immune systems will provide a better understanding of the mechanisms that expose patients to this bacterium.

Detailed Description
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In particular, changes induced by the ECC will be evaluated on: Indoleamine 2,3-dioxygenase activity (IDO) Apoptosis of lymphocytes and dendritic cells Polymorphonuclear neutrophils (PMNs) Myeloid Derived Suppressor Cells (MDSC ) After general anesthesia and arterial catheterization and prior to the start of ECC, blood samples will be taken for flow cytometry studies, for the purification of PMNs and monocytes. The purified PMNs and monocytes will then be used for the measurement of cytokine, phagocytosis and bactericidal production capacities. The morning following surgery, blood samples will be taken and follow the same process.

Official Title
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Immunological and Bacteriological Approaches to the Development of Postoperative Mediastinitis With Staphylococcus Aureus

Conditions
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Surgery, Cardiac, Infection

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients over 18 years of age Patients who require cardiac surgery (valvular and / or coronary) with extracorporeal circulation. Non inclusion criteria Chronic respiratory diseases, Preoperative left ventricular dysfunction (LVEF <50%), Immunosuppression (HIV infection, systemic corticosteroid therapy, history of cancer in the year before surgery), Persons subject to legal protection (safeguard of justice, curatorship, guardianship), Persons deprived of liberty.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with ECC<br>No intervention | Other: No intervention<br>* Patients will undergo standard clinical routine practice in this indication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of plasma IDO activity | IDO activity is evaluated by the Kynurenin / Tryptophan ratio before and after ECC. Enzymatic activities will be measured by high performance liquid chromatography (HPLC) on pre- and post-operative blood tests | Baseline and the morning following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of phagocytosis capacity of PMNs | Comparison before and after ECC | Baseline and the morning following surgery | 
| Variation of bactericidal capacity of PMNs | Comparison before and after ECC | Baseline and the morning following surgery | 
| Variation of phagocytosis capacity of macrophages | Comparison before and after ECC | Baseline and the morning following surgery | 
| Variation of bactericidal capacity of macrophages | Comparison before and after ECC | Baseline and the morning following surgery | 
| Effect of an inhibitor of IDO on phagocytosis capacities of PMNs |  | The day following surgery | 
| Effect of an inhibitor of IDO on bactericidal capacities of PMNs |  | The day following surgery | 
| Effect of an inhibitor of IDO on phagocytosis capacities of macrophages |  | The day following surgery | 
| Effect of an inhibitor of IDO on bactericidal capacities of macrophages |  | The day following surgery | 
| Quantification of lymphocytic apoptosis before and after the ECC | Quantification of apoptosis by flow cytometry | Baseline and the morning following surgery | 
| Quantification of lymphocytic apoptosis in the presence of an inhibitor of IDO | Quantification of apoptosis by flow cytometry | The day following surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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staphylococcus aureus, nosocomial infection