Clinical trial NCT03262558: Mediastinitis and Staphylococcus Aureus
Official title: Immunological and Bacteriological Approaches to the Development of Postoperative Mediastinitis With Staphylococcus Aureus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Surgery, Cardiac
Infection
Keywords: staphylococcus aureus
nosocomial infection
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2017-08-25
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients in the aftermath of an ECC for cardiac surgery are investigated to look for the origin of a hypo-reactivity of PMNs and macrophages during exposure to staphylococcus aureus

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Variation of plasma IDO activity
timeFrame: Baseline and the morning following surgery
Secondary outcomes:
measure: Variation of phagocytosis capacity of PMNs
timeFrame: Baseline and the morning following surgery
measure: Variation of bactericidal capacity of PMNs
timeFrame: Baseline and the morning following surgery
measure: Variation of phagocytosis capacity of macrophages
timeFrame: Baseline and the morning following surgery
measure: Variation of bactericidal capacity of macrophages
timeFrame: Baseline and the morning following surgery
measure: Effect of an inhibitor of IDO on phagocytosis capacities of PMNs
timeFrame: The day following surgery
measure: Effect of an inhibitor of IDO on bactericidal capacities of PMNs
timeFrame: The day following surgery
measure: Effect of an inhibitor of IDO on phagocytosis capacities of macrophages
timeFrame: The day following surgery
measure: Effect of an inhibitor of IDO on bactericidal capacities of macrophages
timeFrame: The day following surgery
measure: Quantification of lymphocytic apoptosis before and after the ECC
timeFrame: Baseline and the morning following surgery
measure: Quantification of lymphocytic apoptosis in the presence of an inhibitor of IDO
timeFrame: The day following surgery
Other outcomes:
Locations:
city: Rennes
country: France
facility: Rennes Hospital University
Study officials:
affiliation: CHU Rennes
name: Jean-Marc TADIE, Md, PhD
role: STUDY_DIRECTOR
References: