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

NCT ID: NCT03869593

Last Updated: 2024-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-03

Study Completion Date

2023-09-01

Brief Summary

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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

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Conditions

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Escherichia Coli Infections Staphylococcus Aureus

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients presenting E. coli and S. aureus bacteremia

Here, to determine the importance of the mutation we will analyze the blood content of patients presenting E. coli and S. aureus bacteremia

Sample analysis

Intervention Type GENETIC

Here, to determine the importance of the mutation we will analyze the blood content of patients presenting E. coli and S. aureus bacteremia

Interventions

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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

Intervention Type GENETIC

Eligibility Criteria

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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

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
Minimum Eligible Age

8 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Johan COURJON, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Nice

Locations

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CHG d'Antibes

Antibes, , France

Site Status

CH Pierre Nouveau

Cannes, , France

Site Status

CHU de Lenval

Nice, , France

Site Status

Countries

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France

References

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Lee CC, Chen SY, Chang IJ, Chen SC, Wu SC. Comparison of clinical manifestations and outcome of community-acquired bloodstream infections among the oldest old, elderly, and adult patients. Medicine (Baltimore). 2007 May;86(3):138-44. doi: 10.1097/SHK.0b013e318067da56.

Reference Type BACKGROUND
PMID: 17505253 (View on PubMed)

Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, Reller LB. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997 Apr;24(4):584-602. doi: 10.1093/clind/24.4.584.

Reference Type BACKGROUND
PMID: 9145732 (View on PubMed)

Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 1;39(3):309-17. doi: 10.1086/421946. Epub 2004 Jul 15.

Reference Type BACKGROUND
PMID: 15306996 (View on PubMed)

Valles J, Palomar M, Alvarez-Lerma F, Rello J, Blanco A, Garnacho-Montero J, Martin-Loeches I; GTEI/SEMICYUC Working Group on Bacteremia. Evolution over a 15-year period of clinical characteristics and outcomes of critically ill patients with community-acquired bacteremia. Crit Care Med. 2013 Jan;41(1):76-83. doi: 10.1097/CCM.0b013e3182676698.

Reference Type BACKGROUND
PMID: 23222266 (View on PubMed)

Herrmann JB, Muenstermann M, Strobel L, Schubert-Unkmeir A, Woodruff TM, Gray-Owen SD, Klos A, Johswich KO. Complement C5a Receptor 1 Exacerbates the Pathophysiology of N. meningitidis Sepsis and Is a Potential Target for Disease Treatment. mBio. 2018 Jan 23;9(1):e01755-17. doi: 10.1128/mBio.01755-17.

Reference Type BACKGROUND
PMID: 29362231 (View on PubMed)

Other Identifiers

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18-AOI-08

Identifier Type: -

Identifier Source: org_study_id

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