Clinical trial NCT03167398: Fecal Microbiota Transplantation for Eradication of CRE
Official title: Fecal Microbiota Transplantation for Eradication of Carbapenem-resistant Enterobacteriaceae Colonization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Antibiotic Resistant Strain
Microbial Colonization
Keywords: fecal microbiota transplantation
carbapenem-resistant enterobacteriaceae
multidrug resistant bacteria
carrier
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
Collaborators: name: Tel-Aviv Sourasky Medical Center
First posted: 2017-05-30
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Antibiotic resistance has emerged world wide and is of major concern. Multi-drug resistant (MDR) bacteria is widely spread and is now 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 authors aim to assess the effects of FMT on colonization and clinical infections with 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 authors 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 timepoint in the following 6 months.


Eligibility criteria: Inclusion Criteria:

* Adult inpatients ≥18 years positive for CRE of any strain and resistance mechanism in rectal surveillance stool samples, with or without CRE clinical samples. A positive rectal swab within one week before randomization will be mandatory.

Exclusion Criteria:

* Pregnant women
* Patients with severe neutropenia (\<100/µl)
* Surgical patients with perfurated viscous

Primary outcomes:
measure: CRE eradication on rectal stool samples
timeFrame: 1 month after intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Health Care Campus
Study officials:
References:
citation: Bar-Yoseph H, Carasso S, Shklar S, Korytny A, Even Dar R, Daoud H, Nassar R, Maharshak N, Hussein K, Geffen Y, Chowers Y, Geva-Zatorsky N, Paul M. Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective. Clin Infect Dis. 2021 Jul 1;73(1):e166-e175. doi: 10.1093/cid/ciaa737.