Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae
Condition: Carbapenem-Resistant Enterobacteriaceae Infection
MeSH terms: Enterobacteriaceae Infections
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): FMT
Intervention type(s): Biological
Intervention description(s): Fecal microbiota in frozen capsules
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment