Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae
- Conditions
- Carbapenem-Resistant Enterobacteriaceae Infection
- Interventions
- Biological: FMT
- Registration Number
- NCT04146337
- Lead Sponsor
- Rambam Health Care Campus
- Brief Summary
2:1, open-label, single center, randomized controlled trial comparing FMT vs. no intervention for CRE carriers,
- Detailed Description
Antibiotic resistance has emerged worldwide and is of major concern leading to multidrug resistant (MDR) bacteria that are widely spread and are a major factor in morbidity and mortality in health-care settings. Among MDRs, carbapenem resistant Enterobacteriaceae (CRE) are of special concern, receiving the highest classification of "urgent threat level" in the US President Report. Consistent mortality rates of 40-50% are observed among inpatients with infections caused by CRE in hospitals worldwide, related mainly to unavailable, delayed or ineffective antibiotic treatment options. The extremely high mortality rates of patients with CRE infections have driven efforts to prevent the acquisition and spread of these bacteria in hospitals. These include screening for carriage, contact isolation of carriers, cohorting, dedicated healthcare staff and other infection control measures. These strategies have been proven as effective but are cumbersome and expensive. In most locations these strategies failed to completely eradicate CRE endemicity. CRE decolonization (eradication of colonization) might offer a double benefit: reducing the risk for the individual carrier to develop an infection due to the resistant strain (by that, potentially lowering the mortality risk) and preventing the bacteria from spreading to other patients, exposing them to the same hazard. Fecal microbiota transplantation (FMT), in which fecal material enriched with commensal microorganisms is transferred from a healthy donor, have proven efficacy in the treatment of recurrent Clostridium difficile infection (CDI) in multiple trails. Major adverse events that has been reported so far are mostly related to the route of administration (aspiration during nasogastric tube administration/colonoscopy). Other adverse events include mostly GI related symptoms (diarrhea, nausea, belching) and are self limited and resolve in few hours. FMT seems to be safe and effective both in immunocompetent and immunocompromised patients. The high efficacy of FMT in the treatment of a multi-drug resistant pathogen such as Clostridium difficile, suggest that it might be an efficient tool for other MDR pathogens (e.g. CRE). The potential of FMT to restore the gut microbiome and compete with residual resistant strains offer a novel way to fight the current MDR epidemic.
The investigators aim to assess the effects of FMT on colonization and clinical infections with CRE. The investigators will apply FMT on a cohort of CRE carriers in a single center in Israel. FMT will be given by capsules for 2 consecutive days followed by rectal sampling at predefined time-point in the following 6 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fecal microbiota transplantation (FMT) FMT FMT regimen: Patients will be given capsulized FMT 15 capsules a day for two consecutive days after a fast of 8 hours before FMT. Stool will be collected before and after the intervention for genomic analysis of CRE strains, analysis of microbiome and metabolome.
- Primary Outcome Measures
Name Time Method CRE eradication 28 days Number of participants achieving CRE eradication at 28 days, defined as 3 consecutive negative rectal cultures, with polymerase chain reaction preformed in the last sample. For patients with clinical infections, eradication definition will include a negative culture from the site of infection, if relevant at the time of eradication.
- Secondary Outcome Measures
Name Time Method Mortality 28-day and 6 months Number of participants who died by 28-day and 6 month
CRE infection 6 months Number of participants with non-bacteremic new clinically-significant CRE infections
CRE eradication rates at day 7, day 14, and 3 & 6 months days 7, 14, months 3, 6 Number of participants achieving CRE eradication rates at day 7, day 14, and 3 \& 6 months
Hospitalization days 6 months Totals days in-hospital
Bacteremia 6 months Number of participants with CRE bacteremia and any bacteremia
Adverse events 6 months Number of participants with: pneumonia within a week after the intervention; dyspeptic complaints collected at the time of rectal sampling; changes in bowel habit including diarrhea and constipation; discontinuation of FMT before completing the study protocol
Trial Locations
- Locations (1)
Rambam Health Care Campus
🇮🇱Haifa, Israel