Clinical trial NCT04699981: Can the Relative Fecal Abundance of BLSE and the Digestive Microbiota be Predictive of the Risk of Infection in a Carrier Patient?
Official title: Can the Relative Fecal Abundance of BLSE and the Digestive Microbiota be Predictive of the Risk of Infection in a Carrier Patient?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Enterobacteria Infections
Lead sponsor: Fondation Hôpital Saint-Joseph
Sponsor class: OTHER
First posted: 2021-01-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Among Enterobacteriaceae, the production of beta-lactamases (ESBLs) is the leading cause of multi-resistance. The first cases of ESBL-producing Enterobacteriaceae (E-ESBL) infections were described in the 1980s and subsequently experienced worldwide dissemination.

Since the turn of the century, the prevalence of E-ESBL infections, especially among Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) has increased dramatically.

The emergence of multidrug-resistant Enterobacteriaceae is currently a real public health problem. The European Antimicrobial Resistance Surveillance Network evaluated, among clinical strains, the rate of resistance to 3rd generation cephalosporins (C3G) at 9.5% for E. coli and 28% for K. pneumoniae. Numerous studies have shown that bacterial colonization is the prerequisite for the occurrence of many infections.

However, the existence of prior colonization does not seem to be the only risk factor for the occurrence of a secondary infection. Therefore, in patients with multidrug-resistant Gram-negative bacillus gastrointestinal carriage there appear to be factors associated with the onset of infection. Several studies have examined the risk factors associated with E-ESBL-related infections in both community-based and healthcare-associated / nosocomial infections. Two main risk factors seem to be associated with E-ESBL infections: prior antibiotic therapy and the existence of invasive devices.

A recent study, carried out on 1288 patients and aimed at validating a predictive score for the occurrence of ESBL-E bacteremia, demonstrated 5 factors associated with the appearance of E-ESBL-linked bacteremia. These factors were: (i) a history of colonization / infection with ESBL-E, (ii) age ≥ 43 years, (iii) recent hospitalization in a region with a high prevalence of ESBL-E, (iv) antibiotic therapy ≥ 6 days in the previous 6 months and (v) the existence of a chronic vascular access.

Recently, a retrospective case-control study conducted in the United States by Augustine et al. Suggested that 5% of cases of bacteremia were related to ESBL-E.

Few studies have looked at risk factors for infection in patients known to be colonized by the digestive system. In a retrospective case-control study, conducted outside the intensive care unit and including pediatric and adult patients, the authors identified 2 factors associated with the occurrence of Ec-ESBL infection in previously colonized patients. These two factors were the prior use of antibiotics with β-lactam antibiotics and β-lactamase inhibitor (s), and urinary catheterization.

In intensive care hospital patients, the occurrence of ESBL-producing enterobacteriaceae infection appears to be a rare event, including in colonized patients.

The work of Ruppé et al. showed a direct link between relative fecal abundance of EScher-producing Escherichia coli and prior antibiotic intake.

This work also demonstrated a link between the value of the relative fecal abundance in Ec-ESBL and the occurrence of a urinary tract infection linked to the same clone. In particular, the authors found that women with a low relative fecal abundance rate (≤ 0.1%) had no risk of developing an Escherichia coli urinary tract infection. Conversely, the risk increased with the relative fecal abundance of Escherichia coli, but with a positive predictive value limited to 57% for relative fecal abundances between 10 and 100%.


Eligibility criteria: Inclusion Criteria:

* Adult patient (≥ 18 years old) hospitalized at the Paris Saint-Joseph Hospital Group or in the intensive care unit of Avicenne hospital, Necker Enfants Malades hospital, Center Sud Francilien, detected as a carrier of enterobacteriaceae in the digestive system ESBL producers
* Patient affiliated to a health insurance plan
* French-speaking patient
* Patient living at home, in EHPAD or retirement home
* Patient or Relative able to give free, informed and express consent

Exclusion Criteria:

* Known patient colonized rectally with ESBL-producing enterobacteria and subjected to antibiotic pressure other than beta-lactams
* Patient participating simultaneously in other intervention research that may interfere with the objectives of the study
* Patient under guardianship or curatorship
* Patient deprived of liberty
* Pregnant or breastfeeding woman

Primary outcomes:
measure: Percentage of EBLSE
timeFrame: Day 60
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint-Joseph
state: Groupe Hospitalier Paris Saint-Joseph
city: Paris
country: France
facility: Hôpital Necker-Enfants malades
state: Groupe Hospitalier Paris Saint-Joseph
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud-Francilien
Study officials:
affiliation: Fondation Hôpital Saint-Joseph
name: Benoit PILMIS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, van Keulen PH, Vandenbroucke-Grauls CM, Meester MH, Verbrugh HA. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004 Aug 21-27;364(9435):703-5. doi: 10.1016/S0140-6736(04)16897-9.
citation: Bruyere R, Vigneron C, Bador J, Aho S, Toitot A, Quenot JP, Prin S, Charles PE. Significance of Prior Digestive Colonization With Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae in Patients With Ventilator-Associated Pneumonia. Crit Care Med. 2016 Apr;44(4):699-706. doi: 10.1097/CCM.0000000000001471.
citation: Dubinsky-Pertzov B, Temkin E, Harbarth S, Fankhauser-Rodriguez C, Carevic B, Radovanovic I, Ris F, Kariv Y, Buchs NC, Schiffer E, Cohen Percia S, Nutman A, Fallach N, Klausner J, Carmeli Y; R-GNOSIS WP4 Study Group. Carriage of Extended-spectrum Beta-lactamase-producing Enterobacteriaceae and the Risk of Surgical Site Infection After Colorectal Surgery: A Prospective Cohort Study. Clin Infect Dis. 2019 May 2;68(10):1699-1704. doi: 10.1093/cid/ciy768.
citation: Zahar JR, Lesprit P, Ruckly S, Eden A, Hikombo H, Bernard L, Harbarth S, Timsit JF, Brun-Buisson C; BacterCom Study Group. Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae. Int J Antimicrob Agents. 2017 Jan;49(1):67-73. doi: 10.1016/j.ijantimicag.2016.09.032. Epub 2016 Nov 16.
citation: Rodriguez-Bano J, Navarro MD, Retamar P, Picon E, Pascual A; Extended-Spectrum Beta-Lactamases-Red Espanola de Investigacion en Patologia Infecciosa/Grupo de Estudio de Infeccion Hospitalaria Group. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012 Jan 15;54(2):167-74. doi: 10.1093/cid/cir790. Epub 2011 Nov 4.
citation: Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH, Milstone AM, Massey CJ, Tamma PD; Antibacterial Resistance Leadership Group. A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum beta-Lactamase-Producing Organism. Clin Infect Dis. 2016 Oct 1;63(7):896-903. doi: 10.1093/cid/ciw425. Epub 2016 Jun 28.
citation: Augustine MR, Testerman TL, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Clinical Risk Score for Prediction of Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae in Bloodstream Isolates. Infect Control Hosp Epidemiol. 2017 Mar;38(3):266-272. doi: 10.1017/ice.2016.292. Epub 2016 Dec 19.