Study of the Nasal Intracellular Reservoir of Staphylococcus Aureus in Patients With S. Aureus Bacteremia (RISTA)

Staphylococcus aureus bacteremia is a serious infection associated with a high mortality rate (with or without associated infective endocarditis (IE)), long hospital stays and multiple complications, due to the terrain in which it occurs and its secondary localization. They may be community-acquired or healthcare-associated infections. Being a carrier of S. aureus is a known risk factor for S. aureus bacteremia. Although several mucosal sites of carriage have been described, screening for carriage is most often carried out at the nasal level, both for reasons of simplicity and because it is the predominant site of carriage of this bacterium. However, S. aureus carriage is a frequent occurrence, affecting around 1/3 of the general population.

Study Overview

• Status: Recruiting
• Conditions: Bacteria Infection Mechanism
• Intervention / Treatment: Diagnostic test: Nasal swab; Biological: Venous sampling; Biological: Antibiotic treatment; Device: Nasal swab; Biological: Intracellular reservoir test

Detailed Description

Long considered an extracellular bacterium, the investigators now know that S. aureus can have an intracellular reservoir. This was initially described in situations of infection (bone infections, vascular infections) and more recently in situations of nasal carriage without associated infection. Among S. aureus carriers, between 15% and 30% have an intracellular reservoir of this bacterium, depending on the study, in patients with no S. aureus infection. For S. aureus carriers with S. aureus infection, there are no data in the literature. The clinical significance of this intracellular reservoir in a carrier situation is currently unknown. The study team was able to demonstrate in vitro that this reservoir was not affected by the mupirocin used in decolonization, and preliminary results suggest that in vivo this reservoir may also be associated with decolonization failure.

Moreover, in vitro, it has been suggested that S. aureus may act on autophagy to promote intracellular survival. Is the intracellular reservoir more frequent in patients with S. aureus bacteremia? Is it associated with a poorer prognosis in S. aureus bacteremia? Is it associated with the production of certain S. aureus intracellular persistence factors? Is it associated with a slowdown in autophagic flow in nasal cells or phagocytes? These questions remain unanswered to this day.

To explore these questions, the investigators plan to conduct a study to assess the frequency of the intracellular S. aureus reservoir (within carriers) in S. aureus bacteremia and in bacteremia to another pathogen (control group). They would also like to study the impact of this reservoir on the persistence of carriage and prognosis (death, duration of bacteremia, length of stay, presence of secondary localizations of bacteremia or endocarditis in the case of S. aureus bacteremia).

• Study Type: Observational
• Enrollment (Estimated): 405

Contacts and Locations

• Study Contact: Name: Elisabeth BOTELHO-NEVERS, MD-PhD; Phone Number: +33 (0)477120764; Email: elisabeth.botelho-nevers@chu-st-etienne.fr
• Study Contact Backup: Name: Amandine Gagneux-Brunon, MD-PhD; Phone Number: +33 (0)477120356; Email: amandine.gagneux-brunon@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France, 42055
    • Recruiting
    • Centre Hospitalier Universitaire de St Etienne
    • Principal Investigator: Elisabeth BOTELHO-NEVERS, MD-PhD
    • Sub-Investigator: Amadine GAGNEUX-BRUNON, MD-PhD
    • Sub-Investigator: Léo SAUVAT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients treated at St-Etienne University Hospital with bacteremia with or without IE. Patients will be assigned to the experimental group in the case of S. aureus bacteremia (whether or not associated with an IE), or to the control group in the case of bacteremia caused by a pathogenic bacterium other than S. aureus (whether or not associated with an IE).

Description

Inclusion Criteria:

• Bacteremia
• Patient affiliated or entitled to a social security plan
• Patient who has signed a consent form to participate in the study.

Exclusion Criteria:

• Antibiotic therapy in place for more than 5 days at the time of inclusion
• Nasal decolonization of S. aureus within 12 months
• Pregnant or breast-feeding women
• Patients under guardianship
• Polymicrobial bacteremia including S. aureus

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental group; Experimental group comprising patients with S. aureus bacteremia with or without IE	Diagnostic test: Nasal swab; Nasal swab to detect nasal carriage of S. aureus; Biological: Venous sampling; Peripheral venous sampling to collect peripheral blood mononuclear cells.; Biological: Antibiotic treatment; Antibiotic treatment for bacteremia (+/- 1 month), in all patients with S. aureus; Device: Nasal swab; A new nasal swab will be taken using the same technique, to see whether or not the carriage persists; Biological: Intracellular reservoir test; In the event of positive carriage, a new intracellular reservoir test will be performed. A search for relapse (new S. aureus infection) or recurrence (S. aureus bacteremia if the 1st bacteremia was due to another pathogen) will be carried out.
Control group; Control group comprising patients with bacteremia with a pathogenic bacterial species other than S. aureus with or without IE.	Diagnostic test: Nasal swab; Nasal swab to detect nasal carriage of S. aureus; Biological: Venous sampling; Peripheral venous sampling to collect peripheral blood mononuclear cells.; Biological: Antibiotic treatment; Antibiotic treatment for bacteremia (+/- 1 month), in all patients with S. aureus; Device: Nasal swab; A new nasal swab will be taken using the same technique, to see whether or not the carriage persists; Biological: Intracellular reservoir test; In the event of positive carriage, a new intracellular reservoir test will be performed. A search for relapse (new S. aureus infection) or recurrence (S. aureus bacteremia if the 1st bacteremia was due to another pathogen) will be carried out.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of intracellular S. aureus carriers at nasal level research	Number of intracellular S. aureus carriers at nasal level research in patients with S. aureus bacteremia associated or not	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of intracellular S. aureus carriers at nasal level research		Day 7
In-hospital mortality rate (%)	In-hospital mortality rate directly related to infection (septic shock, multivisceral failure, death during surgical management related to infection) during bacteremia	Month 1
Mean duration of S. aureus bacteremia (Day)		Month 1
Average number of secondary localizations of S. aureus bacteremia	Clinically diagnosed, or on examination carried out as part of the extension work-up performed as part patient management (Scan, echocardiography, scintigraphy, etc.)	Month 2
Average length of stay in hospital for S. aureus bacteremia (Day)		Month 1
Proportion of nasal S. aureus carriers still carriers at the end of treatment for bacteremia (%)		Month 1
Proportion of nasal S. aureus carriers still carriers one year after the end of treatment for bacteremia (%)		Month 12

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Elisabeth BOTELHO-NEVERS, MD-PhD, CHU Saint-Etienne; Study Chair: Léo SAUVAT, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Estimated): September 13, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Staphylococcus aureus bacteremia
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 20CH025; 2020-A02692-37 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No