Intestinal colonization with extended-spectrum beta-lactamse or carbapenemase producing enterobacteriaceae MedDRA version: 18.1 Level: LLT Classification code 10071097 Term: Beta-lactam antibiotic resistance System Organ Class: 100000004862 MedDRA version: 18.1 Level: LLT Classification code 10069718 Term: Bacterial colonization System Organ Class: 100000004862 MedDRA version: 18.1 Level: LLT Classification code 10028152 Term: Multi-antibiotic resistance System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Diarönt® mono
Pharmaceutical Form: Tablet
INN or Proposed INN: COLISTIN SULFATE
CAS Number: 1264-72-8
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration n
Sponsors
Geneva University Hospitals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult patients (>= 18 years at date of inclusion) - Documented intestinal carriage of ESBL-E and / or CRE by stool culture at baseline (visit 0) - IF COLONIZED WITH ESBL-E ONLY (WITHOUT CRE): At least one episode of symptomatic infection with ESBL-E requiring systemic antibiotic therapy within the last 180 days before date of inclusion (based on the last day of antibiotic therapy for that infection) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: - Pregnancy or planned pregnancy - Breastfeeding - Difficult / impossible follow-up - Allergy or other contraindication to one of the study drugs - Anatomic contraindication to the placement of a nasogastric tube - Recurrent aspirations - Resistance to colistin (defined as MIC> 2 mg/l) of any of the ESBL-E or CRE strains isolated at baseline - Estimated life expectancy = 30 days) or other immunosuppressive medications ? neutropenia with absolute neutrophil count <1000/µL, ? Solid organ transplant recipient ? Hematopoeitic stem cell transplant recepients ? Other causes of severe immunodeficiency - Hospitalization in an Intensive Care Unit - Estimated glomerular filtration rate (CKD-EPI) < 15 ml/min/1.73m2 - Severe food allergy (anaphylaxis, urticaria)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the impact of a five day course of oral colistin and neomycin followed by fecal microbiota transplantation compared to no intervention on detectable intestinal carriage (by stool culture) of extended spectrum beta-lactamase producing and / or carbapenemase producing Enterobacteriaceae 35-48 days after randomization;Secondary Objective: - Assess the impact of a five day course of oral colistin and neomycin followed by FMT compared to no intervention on the susceptibility to colistin of ESBL-E and CRE - Assess the safety and tolerability of a five day course of oral colistin and neomycin followed by FMT for eradication of intestinal ESBL-E and CRE carriage - Assess the impact of a five day course of oral colistin and neomycin followed by FMT compared to no intervention on the intestinal microbiome and resistome over time - Assess the impact of a five day course of oral colistin and neomycin followed by FMT compared to no intervention on the incidence of clinical infections with ESBL-E and CRE over the entire study period - Assess the impact of a five day course of oral colistin and neomycin followed by FMT compared to no intervention on systemic antibiotic use between both study groups - Assess the stability of the microbiome of donor stools after 3, 6, 12 , and 24 months of frozen storage;Primary end point(s): Intestinal carriage of ESBL-E / CRE (absence / presence by stool culture of any ESBL-E and / or CRE with enrichment independent of type of carriage at baseline) 35 to 48 days after randomization;Timepoint(s) of evaluation of this end point: 35 to 48 days after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability • Occurrence of any adverse drug reaction • Occurrence of any adverse event • Occurrence of any serious adverse event • Occurrence of gastrointestinal adverse events Microbiome • Change in intestinal microbiome and resistome in recipients over time • Assess the stability of the microbiome of donor stools after 3, 6, 12 , and 24 months of frozen storage Antibiotic resistance • Isolation of any not intrinsically colistin resistant strain of Enterobacteriaceae during follow-up (MIC> 2mg/l) • Change in colistin MIC between baseline and final follow-up Infections • Occurrence of any clinical infections with ESBL-E and CRE over the entire study period • ESBL-E and CRE infections per 100 patient months at risk (first infection with either) Antibiotic use • Use of any systemic antibiotics during the study period • Use of any antibiotics active against any of the colonizing ESBL-E / CRE strains • Use of any antibiotics active against at least one of the colonizing ESBL-E / CRE strains ;Timepoint(s) of evaluation of this end point: 8 -14 days, 15 -28 days, 35 - 48 days, 5-7and 24 months after randomization | — |
Countries
Israel, Netherlands, Switzerland
Contacts
Public ContactInfection Control Programme
Geneva University Hospitals
Outcome results
None listed