Factors Influencing the Fecal Relative Abundance of ESBL-producing Enterobacteriaceae in Intensive Care (BLSE-REA).

Study of the Fecal Relative Abundance (RA) of ESBL-producing Enterobacteriaceae (ESBL-PE) in Intensive Care (BLSE-REA) : What Are the Factors Influencing the Fecal RA of ESBL-PE in ICU ?

Extended-Spectrum Beta-Lactamases (ESBL)-Producing Enterobacteriaceae (PE) pose a major problem among antimicrobial resistance. The worldwide spread of theses bacteria may be responsible for 10 million death in 2050. Infection with ESBL-PE are associated with a worse prognosis because of delay in the start of adequate antibiotic treatment, especially for severe infections. It has been proposed to identify colonized patients to predict the risk of infection and the risk of nosocomial cross transmission.

This qualitative approach has limit as only 5 to 20% of patients will develop an infection with ESBL-PE. The fecal relative abundance (RA) of ESBL-PE is a ratio of ESBL-PE among enterobacteriaceae that could identify high-risk patients of infection or cross transmission. ESBL-PE RA may be highly variable in patient with antibiotic exposure depending on the molecule received but dynamic data is missing.

The aim of this study is to identify the factor that influence the fecal RA of ESBL-PE in ICU and to evaluate the association between different level of fecal RA and infection or cross transmission with an ESBL-PE.

Study Overview

• Status: Unknown
• Conditions: ESBL-producing Enterobacteriaceae Infections
• Intervention / Treatment: Other: Evaluation of fecal RA and environmental contamination of ESBL-PE carrier in ICU

Detailed Description

Antimicrobial resistance is rising since decades with a risk of million of death in the future. Extended-Spectrum Beta-Lactamases (ESBL)-Producing Enterobacteriaceae (PE) have expanded exponentially since 15 years and represent with Carbapenemase-PE one of the major challenges in resistance control. The burden of ESBL-PE infections is major in intensive care units (ICU) because of the delay to identify an effective antibiotic treatment (highly associated with outcome) and because of a higher risk of nosocomial cross transmission.

Identification of digestive carrier of ESBL-PE is based on a qualitative result that categorize the patient as a carrier or as non-carrier. This result makes it impossible to individualize the measures to be taken for an ESBL-PE carrier.

Prevention of cross transmission has no formal guideline. Some practitioners in ICU have stopped to detect for ESBL-PE carriage (specially when prevalence is low) and other prefer to close the ward (specially during outbreak).

Empiric treatment of most infections in ESBL-PE carrier are based on last-resort antibiotic (i.e. carbapenem) until microbiological results of a clinical simple is available.

A quantitative approach based on fecal relative abundance (RA) of ESBL-PE (ratio between ESBL-PE and enterobacteriaceae) has been proposed to individualize the risk of urinary tract infection (UTI) for ambulatory patients. In this setting, a fecal carriage with a very low RA of ESBL-PE safely rule out a risk of infection with ESBL-PE and patients with a high RA had an increased risk of UTI infection with ESBL-PE. Large variations of RA ESBL-PE carriage was observed and prediction of the level of RA was not possible for a patient.

A high variation in fecal RA of ESBL-PE is probable in ICU because of a high proportion of antibiotic exposure. Using the RA in ICU for ESBL-PE carrier could make it possible to identify patients who need for carbapenem in their empiric treatment and those who need continuing contact precautions to prevent cross transmission.

The aim of this study is to identify the factor that influence the fecal RA of ESBL-PE in ICU and to evaluate the association between different level of fecal RA and infection or cross transmission with an ESBL-PE.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Positive sample for ESBL-PE at admission of during ICU stay
• Patient's or relative's consent

Exclusion Criteria:

• Women pregnant, parturient or breast-feeding during the study period
• Patient deprived of liberty by judicial or administrative decision
• Patient undergoing psychiatric care under duress
• Patient subject to a legal protection measure
• Patient with no social security coverage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Evaluation of patient and patient-care environment ESBL; ESBL-PE carriers included in the study will be sampled for evaluation of their fecal RA of ESBL-PE on day 0, 3, 5, 7, 10, 14 and weekly till day 30 or their discharge from ICU. Urine and respiratory samples will be collected on the same day to identify multiple-site colonization with ESBL-PE. Seven samples of patient care environment will be performed 2-times a week till day 30 or discharge of the patient from the ICU.

Other: Evaluation of fecal RA and environmental contamination of ESBL-PE carrier in ICU; ESBL-PE carriers included in the study will be sampled for evaluation of their fecal RA of ESBL-PE on day 0, 3, 5, 7, 10, 14 and weekly till day 30 or their discharge from ICU. Urine and respiratory samples will be collected on the same day to identify multiple-site colonization with ESBL-PE. Seven samples of patient care environment will be performed 2-times a week till day 30 or discharge of the patient from the ICU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in fecal ESBL-PE RA in the ICU	Factors associated with changes in the RA of ESBL-PE fecal carriage will be analyzed. RA is expressed by the ratio of ESBL-PE and total enterobacteriaceae.	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between changes in ESBL-PE RA in fecal samples and ESBL-PE infection	Looking for a threshold of ESBL-PE RA in fecal sample and a high risk of ESBL-PE infection	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.
Association between changes in ESBL-PE RA in fecal samples and ESBL-PE cross-transmission	Is there an association between a high ESBL-PE RA in fecal samples and cross-transmission	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.
Association between changes in ESBL-PE RA in fecal samples and multiple-site colonization	Is there an association between a high ESBL-PE RA in fecal samples and multiple-site colonization	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.
Association between changes in ESBL-PE RA in fecal samples and patient care environment contamination with ESBL-PE	Is there an association between a high ESBL-PE RA in fecal samples and patient care environment contamination with ESBL-PE	Twice a week till day 30.
Comparison of changes in ESBL-PE RA between different bacteria species during ICU stay	Are there differences of RA between different species of ESBL-PE	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.
Incidence of high level of EBSL-PE RA in ICU fecal carriers	High level of RA is defined by a ratio of ESBL-PE on total enterobacteriaceae > 0.2	Day 0, 3, 5, 7, 10, 14 and weekly till day 30.

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Intensive care unit; Carriage; Extended-spectrum beta-lactamase; Cross transmission; Fecal relative abundance
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections
• Other Study ID Numbers: RCB 2019-A02861-56

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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