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

NCT03869593 | Terminated

• 1 other identifier: 18-AOI-08
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 3

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.

Conditions

Escherichia Coli Infections; Staphylococcus Aureus

Outcome Measures

Primary Outcomes (2)

• Establish an association between mutations in some inflammasomes and occurrence of E. coli associated with sepsis.

  1 hour

• Establish an association between mutations in some inflammasomes and occurrence of S. aureus bacteremia associated with sepsis.

  1 hour

Study Arms (1)

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

Genetic: Sample analysis

Interventions

Sample analysis GENETIC

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

Patients presenting E. coli and S. aureus bacteremia

Eligibility Criteria

• Age: 8 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with S. aureus or E. coli bacteremia defined by at least one positive blood culture

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (3)

CHG d'Antibes

Antibes, France

Location

CH Pierre Nouveau

Cannes, France

Location

CHU de Lenval

Nice, France

Location

Related Publications (6)

• 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.

  PMID: 17505253 BACKGROUND

• 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.

  PMID: 9145732 BACKGROUND

• 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.

  PMID: 15306996 BACKGROUND

• 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.

  PMID: 23222266 BACKGROUND

• 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.

  PMID: 29362231 BACKGROUND

• Doye A, Chaintreuil P, Lagresle-Peyrou C, Batistic L, Marion V, Munro P, Loubatier C, Chirara R, Sorel N, Bessot B, Bronnec P, Contenti J, Courjon J, Giordanengo V, Jacquel A, Barbry P, Couralet M, Aladjidi N, Fischer A, Cavazzana M, Mallebranche C, Visvikis O, Kracker S, Moshous D, Verhoeyen E, Boyer L. RAC2 gain-of-function variants causing inborn error of immunity drive NLRP3 inflammasome activation. J Exp Med. 2024 Oct 7;221(10):e20231562. doi: 10.1084/jem.20231562. Epub 2024 Aug 30.

  PMID: 39212656 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

2 samples of blood will be collected during a routine blood test. A sample will allow the analysis of the study, the second will join a biobank.

MeSH Terms

Conditions

Escherichia coli Infections; Staphylococcal Infections

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gram-Positive Bacterial Infections

Study Officials

• Johan COURJON, MD

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 11, 2019
• Study Start: June 3, 2019
• Primary Completion: March 22, 2022
• Study Completion: September 1, 2023
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)