Role of the NLRP3 Inflammasome in Escherichia Coli and Staphylococcus Aureus Bacteria

Terminated

• Conditions: Escherichia Coli Infections; Staphylococcus Aureus
• Interventions: Genetic: Sample analysis

• Registration Number: NCT03869593
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief Summary

Our previous studies delineate a novel pathway of immune activation in animals that the investigators have named Anti-Virulence Immunity (AVI). Using a mice model of bacteremia, the investigators have demonstrated that Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) activity is sensed by the immune system. This immune sensing results in a rapid bacterial clearing during bacteremia triggered by uropathogenic E. coli-expressing CNF1. The investigators already confirmed the involvement of one inflammasome using macrophages isolated from Knock-out mice. The investigators have recently determined the conservation in human monocytes of the interleukin -1beta maturation triggered by CNF1 and observed the heterogeneous capacity of monocytes to respond to the CNF1 treatment depending on the donors. Here, to determine the importance in natura of AVI the investigators will analyze the blood content of patients presenting E. coli and S. aureus bacteremia. The DNA of monocytes isolated from patients will be extracted and various genes implicated in the activity of various inflammasomes will be sequenced to identify mutations that could explain the susceptibility to bacteremia or a specific clinical presentation, i.e. requirement of a management in ICU because of organ failure.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-03-04
• Study First Submitted QC: 2019-03-07
• Study First Posted: 2019-03-11
• Study Start: 2019-06-03
• Primary Completion: 2022-03-22
• Study Completion: 2023-09-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patient with S. aureus or E. coli bacteriostatic bacteremia defined by at least one positive blood culture bottle
• Patient requiring a blood test as part of his bacteremia
• not subject to a judicial protection measure
• Signature of the non-opposition of consent (for minor patients signed by one of the parents or the representative of the parental authority)
• Affiliation to social security

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Exclusion Criteria

• Immunocompromised patient defined by:

  • current immunosuppressive therapies: corticosteroids, chemotherapy, biotherapy
  • solid organ transplant patient or hematopoietic stem cell transplant
  • chemotherapy-induced neutropenia
  • Congenital immune deficiency

• bacteremia related to a peripheral or central catheter

• Urinary obstruction not lifted within the first 24 hours of management

• Intra-abdominal infection collected undrained in the first 24 hours of management

• primary infectious focus represented by mechanically ventilated pneumonia

• Pregnant or lactating woman

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients presenting E. coli and S. aureus bacteremia	Sample analysis	Here, to determine the importance of the mutation we will analyze the blood content of patients presenting E. coli and S. aureus bacteremia

Primary Outcome Measures

Name	Time	Method
Establish an association between mutations in some inflammasomes and occurrence of S. aureus bacteremia associated with sepsis.	1 hour
Establish an association between mutations in some inflammasomes and occurrence of E. coli associated with sepsis.	1 hour

Trial Locations

Locations (3)

CH Pierre Nouveau; 🇫🇷 Cannes, France

CHU de Lenval; 🇫🇷 Nice, France

CHG d'Antibes; 🇫🇷 Antibes, France