Mediastinitis and Staphylococcus Aureus (MEDIASTAPH)

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

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.

Study Overview

• Status: Completed
• Conditions: Infection; Surgery, Cardiac
• Intervention / Treatment: Other: No intervention

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.

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Rennes Hospital University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with ECC; No intervention	Other: No intervention; Patients will undergo standard clinical routine practice in this indication

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Study Director: Jean-Marc TADIE, Md, PhD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): September 29, 2019

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 25, 2017

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: staphylococcus aureus; nosocomial infection
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Mediastinal Diseases; Thoracic Diseases; Mediastinitis
• Other Study ID Numbers: 35RC16_9886

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No