Clinical trial NCT03374371: Invasive Markers of Staphylococcus Epidermidis
Official title: Identification of Genomic Markers Associated With the Invasiveness of Staphylococcus Epidermidis Strains Responsible for Infections
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Staphylococcus Epidermidis Positive Blood Culture
Keywords: Staphylococcus epidermidis Infection
Staphylococcus epidermidis Contamination
intravascular device
implanted material
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-12-15
Enrollment: 320
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Population 1 (bacteraemia related to intravascular devices) : patients hospitalized for at least 48 hours including new-borns

Population 2 (infections of materials) : patients carrying medical devices implanted following an act of surgery (orthopedic, cardiac or neurosurgery)

Brief summary: The purpose of the study is to identify biomarkers allowing the distinction between invasive and non-invasive strains of Staphylococcus epidermidis. This distinction is important to determine if the patient is infected and, as a consequence, if an antibiotic treatment is required.

Detailed description: In the hospital, a large proportion of bacteraemia and implantable medical device infections are caused by Staphylococcus epidermidis. This microorganism is the most abundant on human skin and all patients are carriers. Its remarkable ability to form biofilms on most materials explains that catheter-related infections are by far the most common.

S. epidermidis infections are difficult to treat because most strains are multi-resistant and antibiotics are less effective in the presence of biofilms.

In addition, S. epidermidis poses a major diagnostic problem because it is also the first source of contamination of blood culture sample and intraoperative samples (in case of suspected infection of orthopedic material in particular). Thus, when a sample is positive for S. epidermidis, there is less than a 25% chance that it reflects true bacteremia in the patient and 30% of patients would inappropriately receive vancomycin following contaminated blood cultures. Differentiating a contamination of a blood or intraoperative sample from true S. epidermidis infection is therefore crucial for patient management because unnecessary antibiotic therapy is potentially responsible for the emergence of resistant strains, toxicity and additional costs.

The objective of this study is to identify the genetic markers that make it possible to differentiate the strains causing infections from the strains causing contamination by comparing their genomes using high throughput sequencing.

Eligibility criteria: Inclusion Criteria:

CASE Inclusion Criteria:

Population 1: nosocomial bacteraemia associated with intravascular devices

1. Hospitalized patient with intravascular device (peripheral or central, venous or arterial, short or long duration) for at least 48 hours before the development of bacteraemia
2. Presenting a definite infection with S. epidermidis according to the categorization criteria,

Sub-Population 1A:

3a) Aged less than 28 days (New-born)

Sub-population 1B:

3b) Aged 28 days or more

Population 2: nosocomial infections of implanted material

1. An operated patient carrying implanted equipment following orthopaedic surgery, following cardiac surgery or following neurosurgery,
2. Presenting a definite infection with S. epidermidis according to the categorization criteria occurring in the year following surgery

CONTROL Inclusion Criteria:

Population 1: carrier of intravascular devices

1. Hospitalized patient with intravascular device (peripheral or central, venous or arterial, short or long duration) for at least 48 hours before positive blood culture with S. epidermidis
2. Certain contamination with S. epidermidis according to the categorization criteria,

Sub-Population 1A:

3a) Aged less than 28 days (Newborn)

Sub-population 1B:

3b) Aged 28 days or more

Population 2: carrier of implanted material

1. An operated patient carrying implanted equipment following orthopedic surgery, following cardiac surgery or following neurosurgery,
2. Presenting a certain contamination to S. epidermidis according to the categorization criteria occurring in the year following surgery

Exclusion Criteria:

CASE Exclusion Criteria Population 1: nosocomial bacteremia associated with intravascular devices

1. Opposition of the patient or the holders of parental authority (minor patients)
2. Patient with polymicrobial infection
3. Patient with a colonized catheter (positive catheter end culture \<103UFC / mL) with no clinical signs of local or general infection and with sterile peripheral blood cultures
4. Patient with local catheter infection (positive catheter end culture\> 103UFC / mL) with local inflammatory signs only and with sterile peripheral blood cultures

Population 2: nosocomial infections of implanted material

1. Opposition of the patient or the holders of parental authority (minor patients)
2. Patient with an infection of material concomitant with a catheter-related infection

CONTROL Exclusion Criteria

Populations 1 and 2:

Opposition of the patient or the holders of parental authority (minor patients)

Primary outcomes:
measure: genetic markers of S. epidermidis
timeFrame: at the time of the positive sampling of S. epidermidis
Secondary outcomes:
measure: Correlation of the genotype with the characteristics of the infections
timeFrame: at the time of the positive sampling of S. epidermidis
measure: Intra-hospital cross-transmission detection
timeFrame: at the time of the positive sampling of S. Epidermidis
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
state: Ile De France
Study officials:
affiliation: Assistance Public Hôpitaux de Paris (APHP)
name: Anne JAMET, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jamet A, Guglielmini J, Brancotte B, Coureuil M, Euphrasie D, Meyer J, Roux J, Barnier JP, Bille E, Ferroni A, Magny JF, Bole-Feysot C, Charbit A, Nassif X, Brisse S. High-Resolution Typing of Staphylococcus epidermidis Based on Core Genome Multilocus Sequence Typing To Investigate the Hospital Spread of Multidrug-Resistant Clones. J Clin Microbiol. 2021 Feb 18;59(3):e02454-20. doi: 10.1128/JCM.02454-20. Print 2021 Feb 18.