From Commensalism to Pathogenicity: Exploring the Pathophysiology of Bacteremia to Better Understand Enterococcus Faecalis Infective Endocarditis

NCT07313865 | Not Yet Recruiting

• 1 other identifier: RBHP 2025 VIDAL
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Enterococci are pathobionts of the human intestinal microbiota: they colonize the gastrointestinal tract as well as the skin, urine, wounds, bile, the oral cavity and endodontic canal, and medical devices (urinary catheters, venous catheters, etc.). They are responsible for urinary, dental, bloodstream, endocardial, biliary, and gastrointestinal infections. Enterococcus faecalis is the enterococcus most frequently isolated from clinical specimens. It is the third leading cause of infective endocarditis (infection of the cardiac valves) and the leading cause of endocarditis following TAVI (transcatheter aortic valve implantation via the femoral route). E. faecalis infective endocarditis (EFIE) is severe and difficult to treat, with a particularly high relapse rate despite appropriate antibiotic therapy. Cardiac valve contamination is always secondary to E. faecalis bacteremia, particularly in cases of isolated E. faecalis bacteremia (EFIB), defined by the absence of an identifiable portal of entry. Once in the bloodstream, the bacterium adheres to the valvular endothelium (healthy or damaged) through specific virulence factors, including endocarditis- and biofilm-associated pili (ebp), the collagen adhesin Ace, and aggregation substance (Agg). The classical portals of entry for EFIE are infections of the urinary tract and the gastrointestinal tract. However, despite extensive investigations, the source of infection remains unidentified in more than 50% of cases. An imbalance of the intestinal microbiota, leading to overgrowth and subsequent translocation of E. faecalis from the digestive tract into the bloodstream, could explain the absence of an identifiable portal of entry during routine clinical and paraclinical evaluations. This plausible hypothesis remains largely unexplored to date. A better understanding of the underlying pathophysiology-particularly gut dysbiosis and the pathogen's capacity for intestinal translocation-could improve the prevention of EFIE occurrence and relapse.

Conditions

Infective Endocarditis (IE)

Keywords

Enterococcus faecalis; Bacteremia; Dysbiosis; Pathophysiology; Virulence factors

Outcome Measures

Primary Outcomes (1)

• Qualitative and quantitative bacterial composition of the intestinal microbiota (molecular microbiology/PCR).

  From enrollment to the collection of the four swabs: 24 to 48 hours.

Secondary Outcomes (4)

• Mapping of E. faecalis colonization (urinary, digestive, and/or cutaneous) in patients diagnosed with E. faecalis bacteremia (EFIB);

  From enrollment to the collection of the four swabs: 24 to 48 hours.

• Genomic characterization through core genome analysis of E. faecalis strains isolated from colonization sites and from blood cultures in the same patient diagnosed with EFIB;

  From enrollment to the collection of the four swabs: 24 to 48 hours.

• Whole-genome characterization of E. faecalis strains isolated from colonization sites and those recovered from blood cultures in patients with EFIB;

  From enrollment to the collection of the four swabs: 24 to 48 hours.

• Description of potential portals of entry for enterococci at the end of hospitalization for EFIB.

  From enrollment to the collection of the four swabs: 24 to 48 hours.

Study Arms (2)

Cases

OTHER

Collection of four swabs (two rectal swabs, one oral swab, and one skin swab from the inguinal fold).

Biological: Microbiological sampling (swab collection)

Controls

OTHER

Collection of a single rectal swab.

Biological: Microbiological sampling (swab collection)

Interventions

Microbiological sampling (swab collection) BIOLOGICAL

Participants in the case group will undergo microbiological sampling consisting of four swabs: two rectal swabs, one oral swab, and one skin swab from the inguinal fold. Participants in the control group will undergo a single rectal swab. The samples will be collected for microbiological analysis.

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years and older;
• Capable of giving informed consent;
• Affiliated with a social security system;
• Hospitalized with at least one positive blood culture for Enterococcus faecalis, without an obvious clinical entry point after physical examination and initial routine investigations (BIEF group);
• Hospitalized for another bacteremia, without an obvious clinical entry point after initial routine investigations (Control group);
• Receiving antibiotic therapy that was started less than 48 hours ago

You may not qualify if:

• Refusal to participate in the study;
• Pregnant or breastfeeding women;
• Individuals under guardianship, curatorship, deprived of liberty, or under judicial protection;

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU de Clermont-Ferrand

Clermont-Ferrand, France, 63000, France

Location

MeSH Terms

Conditions

Endocarditis; Bacteremia; Dysbiosis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Magali VIDAL

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

334.73.754.963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: January 2, 2026
• Study Start: January 2, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 9, 2026

Record last verified: 2025-12

Locations

FR (1)