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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01703299
First received: September 25, 2012
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition
Carbapenem-induced Resistance

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    faecal bacterial growth on selective culture media


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    faecal bacterial growth on selective culture media


Biospecimen Retention:   Samples Without DNA

faeces, bacterial DNA


Enrollment: 33
Study Start Date: October 2012
Study Completion Date: March 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
imipenem-treated patients
imipenem-treated patients
ertapenem-treated patients
ertapenem-treated patients

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

hospitalized patients initiating a carbapenem treatment

Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01703299

Locations
France
Hôpital Beaujon
Clichy, France, 92110
Hôpital Louis Mourier
Colombes, France, 92700
Hôpital Bichat-Claude Bernard
Paris, France, 75018
Hôpital Saint-Louis
Paris, France, 75475
Hôpital Paul Brousse
Villejuif, France, 94800
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Antoine Andremont, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01703299     History of Changes
Other Study ID Numbers: CRC11016
Study First Received: September 25, 2012
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
imipenem
ertapenem
resistance
commensal flora

Additional relevant MeSH terms:
Imipenem
Ertapenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014