Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments (ERIC)

May 12, 2015 updated by: Assistance Publique - Hôpitaux de Paris
The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more common due to the increased prevalence in the hospital and community of extended spectrum β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure towards emergence of strains which are also resistant to carbapenems, placing patients in a catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake preventive measures to preserve their effectiveness. The aim of the study is to evaluate and describe the emergence of carbapenem-induced resistant GNB in patient intestinal microflora.

Study Overview

Status

Completed

Conditions

Detailed Description

The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more common due to the increased prevalence in the hospital and community of extended spectrum β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure towards emergence of strains which are also resistant to carbapenems, placing patients in a catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake preventive measures to preserve their effectiveness.

Hypotheses: Carbapenems induce in treated patients the emergence of resistant GNB in intestinal flora and have an impact on colonization resistance of the gut microbiota.

Primary objective: To determine the frequency of emergence of carbapenems resistant GNB in the intestinal flora at the end of a treatment by imipenem or ertapenem.

Secondary objective(s):

  • Assess the presence of carbapenem resistant GNB in the intestinal flora before treatment.
  • Evaluate the presence and / or persistence of carbapenem resistant GNB in the intestinal flora on day 3 of treatment, and 15 days and 1 month after the end of treatment.
  • Determine the molecular mechanisms of resistance of strains of interest.
  • Describe the gastrointestinal tract colonization by non-commensal microorganisms before and after treatment (impact on colonization resistance).
  • Describe the characteristics of patients with emergence of resistance compared to patients who do not.
  • Proper conservation of stool of 10 patients for metagenomic and/or metatranscriptomic analysis of changes in the intestinal flora.

Primary endpoint: Presence of carbapenem resistant GNB in the stool at the end of treatment in patients who did not before, after culture on selective media.

Secondary endpoints:

  • Presence of carbapenem resistant GNB in stools before treatment, at day 3 and 15 days and 1 month after stopping treatment, after culture on selective media.
  • PCR and sequencing of resistance genes from strains of interest.
  • Colonization of the digestive tract by non-commensal microorganisms before and after treatment.
  • Characteristics of patients with or without emergence of resistance.

Study Type

Observational

Enrollment (Actual)

35

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clichy, France, 92110
        • Hopital Beaujon
      • Colombes, France, 92700
        • Hôpital Louis Mourier
      • Paris, France, 75018
        • Hopital Bichat-Claude Bernard
      • Paris, France, 75475
        • Hopital Saint-Louis
      • Villejuif, France, 94800
        • Hopital Paul Brousse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

hospitalized patients initiating a carbapenem treatment

Description

Inclusion Criteria:

  • age> or = 18 years old
  • hospitalized
  • initiating a treatment by imipenem or ertapenem-
  • faeces harvested before the beginning of treatment
  • written informed consent from the patient or from a relative if the patient is incapable of expressing his/her consent
  • reachable by phone after hospitalization (only for patients able to express their consent).

Exclusion Criteria :

  • hospitalized in intensive care unit
  • concomitant antibiotic treatment (except aminosid or vancomycin for less than 4 days).

Secondary exclusion criteria :

  • introduction of other antibiotics during carbapenem treatment (except vancomycin or aminosid)
  • vancomycin treatment for more than 4 days during carbapenem treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
imipenem-treated patients
ertapenem-treated patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
presence of carbapenem-resistant gram-negative bacteria at the end of carbapenem treatment in faeces of patients who were free of carbapenem-resistant gram-negative bacteria before the beginning of treatment
Time Frame: at the end of carbapenem treatment period which usually lasts between 2 and 15 days
faecal bacterial growth on selective culture media
at the end of carbapenem treatment period which usually lasts between 2 and 15 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
presence of carbapenem-resistant gram-negative bacteria in patient faeces before carbapenem treatment, at day 3 of carbapenem treatment and at day 15 et day 30 after the end of carbapenem treatment
Time Frame: before, at day 3 of carbapenem treatment and at day 15 and day 30 after the end of carbapenem treatment
faecal bacterial growth on selective culture media
before, at day 3 of carbapenem treatment and at day 15 and day 30 after the end of carbapenem treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Antoine Andremont, MD, PhD, Assistance Publique - Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

September 25, 2012

First Submitted That Met QC Criteria

October 7, 2012

First Posted (Estimate)

October 10, 2012

Study Record Updates

Last Update Posted (Estimate)

May 13, 2015

Last Update Submitted That Met QC Criteria

May 12, 2015

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CRC11016

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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