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

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

Status
Not yet recruiting
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07313865
Acronym
BAC-ENDO
Enrollment
90
Registered
2026-01-02
Start date
2026-01-02
Completion date
2028-12-31
Last updated
2026-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infective Endocarditis (IE)

Keywords

Enterococcus faecalis, Bacteremia, Dysbiosis, Pathophysiology, Virulence factors

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.

Interventions

BIOLOGICALMicrobiological sampling (swab collection)

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.

Sponsors

University Hospital, Clermont-Ferrand
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* 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

Exclusion criteria

* Refusal to participate in the study; * Pregnant or breastfeeding women; * Individuals under guardianship, curatorship, deprived of liberty, or under judicial protection; * Antibiotic therapy for the current infectious episode started more than 48 hours prior to inclusion.

Design outcomes

Primary

MeasureTime frame
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

MeasureTime frame
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.

Countries

France

Contacts

Primary ContactLise Laclautre
promo_interne_drci@chu-clermontferrand.fr334.73.754.963

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026