Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments (ERIC)
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments|
- 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
- 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
|Study Start Date:||October 2012|
|Study Completion Date:||March 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01703299
|Clichy, France, 92110|
|Hôpital Louis Mourier|
|Colombes, France, 92700|
|Hôpital Bichat-Claude Bernard|
|Paris, France, 75018|
|Paris, France, 75475|
|Hôpital Paul Brousse|
|Villejuif, France, 94800|
|Principal Investigator:||Antoine Andremont, MD, PhD||Assistance Publique - Hôpitaux de Paris|