Antimicrobial Combination Therapy for Treatment of Enterococcus Faecalis Bacteremia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorIRCCS Azienda Ospedaliero-Universitaria di Bologna
About this trial
Prospective, multicenter, national, observational pharmacological study on the evaluation of efficacy of appropriate monotherapy vs combination treatment for non-complicated Enterococcus faecalis (EF) bloodstream infection (BSI) and identification of gut microbiota fingerprint of patients with EF-BSI correlated to antimicrobial treatment and clinical outcome
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult (≥18 years)
Monomicrobial EF-BSI
Receipt of ≥ 5 days of at least one in vitro active drug (ampicillin, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, vancomycin, teicoplanin, daptomycin and linezolid) with or without a synergistic drug (ceftriaxone, gentamycin, streptomycin), at common suggested dosages for EF-BSI in empirical or definitive therapy
Written informed consent
Disqualifiers
Short term (within 3 days from BSI) mortality
Other concomitant infection
Trial population
All adult patients (≥ 18 years) with primary Enterococcus faecalis monomicrobial bloodstream infection
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
510 Participants
are grouped into 1 trial groupGroup A: Adult with Enterococcus faecalis monomicrobial bloodstream infection
Trial outcomes
Primary outcomes
1
Evaluation of Clinical Cure and Improvement Rates for EF-BSI
The clinical cure and improvement rates will be evaluated for patients undergoing mono therapy and combination therapy for EF-BSI.
Time frame
Up to 6 weeks from patient enrollment, with bacterial strains isolated at baseline2
Comparison of Clinical Outcomes Between Mono Therapy and Combination Therapy
A comparison of clinical outcomes between mono therapy and combination therapy in terms of clinical cure, improvement, and any adverse events.
Time frame
Up to 6 weeks from patient enrollment, with bacterial strains isolated at baseline3
Validation of In Vitro Synergy Tests
To validate the in vitro synergy or antagonism of antimicrobial combinations tested in the laboratory, correlating these results with clinical outcomes. In vitro synergy tests will be conducted to evaluate the interaction between antimicrobial combinations, and the results of these tests will be correlated with the clinical outcomes of the patients.
Time frame
Up to 6 weeks from patient enrollment, with bacterial strains isolated at baselineSecondary outcomes
1
Genotypic Analysis of E. faecalis
To explore how the genotypic (e.g., resistance and virulence genes) and phenotypic traits of E. faecalis strains influence infection severity, antimicrobial treatment response, and clinical outcomes. Define the prognostic and predictive value of these genotypic and phenotypic traits based on antimicrobial treatment and clinical outcomes. Genomic analyses will be conducted to identify antimicrobial resistance determinants, clonal relationships through multilocus sequence typing (MLST), and virulence factor genes for To explore how the genotypic traits (e.g., antimicrobial resistance and virulence genes) of E. faecalis strains influence infection severity, antimicrobial treatment response, and clinical outcomes. Weekly genomic analyses will be conducted to identify antimicrobial resistance determinants, clonal relationships through multilocus sequence typing (MLST), and virulence factor genes for each E. faecalis genome.
Time frame
From enrollment to the end of the follow-up at three months2
Phylogenetic Relationship and Clonal Diversity
A phylogenetic tree will be constructed based on the core genome of clinical E. faecalis isolates. This will allow the identification of clonal relationships and shared genetic factors among the strains. A deeper genetic analysis will also be performed to explore genetic factors that may influence infection outcomes.
Time frame
From enrollment to the end of the follow-up at three months3
Correlation Between Genotypic/Phenotypic Traits and Clinical Outcome
The prognostic and predictive value of the genotypic (e.g., resistance and virulence genes) and phenotypic traits of E. faecalis will be defined in relation to antimicrobial treatment and clinical outcomes. A comprehensive E. faecalis genomic database will be created to correlate these traits with infection severity, antimicrobial treatment, and clinical outcomes. The correlation will be explored through weekly genomic analyses and clinical data review.
Time frame
From enrollment to the end of the follow-up at three months4
Gut Microbiota Fingerprint Analysis in EF-BSI Patients
To compare the gut microbiota fingerprint of patients with E. faecalis bloodstream infections (EF-BSI) and correlate it with antimicrobial treatment and clinical outcomes. Faecal samples will be collected during antimicrobial therapy and 90 days after therapy withdrawal. These samples will be analyzed for 16S rRNA and the relative microbial composition. Clinical conditions, diet, infection relapse after therapy withdrawal, and their correlation with antimicrobial treatment and faecal abundance will also be evaluated.
Time frame
From enrollment to the end of the follow-up at three monthsSponsors and contacts
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Source ClinicalTrials.gov