The Effect of Fecal Microbiota Transplantation on the Decolonization of Multidrug-resistant Organisms

The Effect of Fecal Microbiota Transplantation on the Decolonization of Carbapenem-resistant Enterobacteriaceae or Vancomycin-resistant Enterococci in the Gut

The purpose of this study is to assess the effect of fecal microbiota transplantation for the decolonization of carbapenem-resistant Enterobacteriaceae or vancomycin-resistant Enterococci in the gut.

Study Overview

• Status: Recruiting
• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection; Vancomycin-Resistant Enterococcal Infection
• Intervention / Treatment: Other: fecal microbiota transplantation

Detailed Description

This study is a prospective observational cohort study exploring the decolonization effect of Fecal Microbiota Transplantation (FMT) in patients colonized with Carbapenem-resistant Enterobacteriaceae (CRE) and Vancomycin-resistant Enterococci (VRE).

Patients who have provided written consent for participation in the study will be required to maintain fasting starting from the evening before the procedure, after discontinuing broad-spectrum antibiotics for a minimum of 3-7 days. Subsequently, a bowel preparation will be carried out twice - the evening before and the morning of the procedure. Once the bowel preparation is complete, 1 hour before the procedure, patients will receive loperamide to reduce bowel movements and then proceed to the endoscopy suite.

Fecal microbiota transplantation (FMT) will be carried out with the acquired frozen donor stool, which will be thawed for 2 hours at room temperature following purchase and delivery from a stool bank, under the consent and supervision of the patient or guardian. Frozen stool from carefully screened donors who have passed the rigorous screening of both Stage 1 clinical assessment and Stage 2 laboratory tests (including evaluation for antibiotic resistance organisms) will be supplied from a stool bank of Microbiotix inc. (Hyun Soo Seo, et al. Ann Lab Med 2021;41:424-428).

The FMT procedure will be conducted in collaboration with the research team in the Division of Gastroenterology. During the procedure, no tissue biopsy or excessive endoscope insertion will be performed. The FMT involves the simple infusion of thawed donor stool into the terminal ileum under colonoscopy, which takes approximately 5-10 minutes. The procedure carries minimal risk of bleeding, perforation, or aspiration. In most cases, it will be performed under sedation with colonoscopy. If smooth insertion of the colonoscope or proper visualization of the colon is hindered, or if colonic preparation is not successful, Esophagogastroduodenoscopy (EGD) will be performed with sedation, and thawed donor stool will be infused into the third portion of the duodenum. This procedure also poses minimal risk of regurgitation or aspiration due to its anatomical and physiological characteristics. After the procedure, the lower extremities will be elevated by about 30 degrees to prevent the transplanted stool from exiting. A one-day fasting period will be maintained after the procedure to facilitate successful engraftment of the transplanted stool, followed by the gradual resumption of a regular diet. Following FMT, repeated rectal swab cultures will be conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-7 day intervals.

In cases where encapsulated fecal material is used for FMT, it will be ingested along with high-acid cranberry or orange juice. The capsules are specially designed to dissolve in low-acidic environments, allowing them to reach the terminal ileum for safe administration without the need for bowel preparation. On the first day, 15 capsules will be consumed, followed by another 15 capsules on the second day, for a total of 30 capsules. Subsequently, repeated rectal swab tests will be conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-day intervals.

According to patient random allocation, fecal samples and clinical metadata will be periodically collected (prior to FMT, 1 month, 3 months, 6 months, and 12 months after FMT) from both recipients and donors. These collected samples will undergo full-length 16S rRNA sequencing and shotgun metagenomic sequencing to comprehensively analyze the gut microbiome. Through this analysis, the aim is to elucidate the intestinal microorganisms associated with decolonization outcomes and mechanisms.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Seung Soon Lee, MD; Phone Number: +82-33-240-5599; Email: hushh93@gmail.com
• Study Contact Backup: Name: Ki Tae Suk, MD, PhD; Phone Number: +82332405826; Email: ktsuk@hallym.or.kr

Study Locations

• Korea, Republic of
  • Gangwon-do
    • Chuncheon, Gangwon-do, Korea, Republic of, 24253
      • Recruiting
      • Chuncheon Sacred Heart Hospital
      • Contact: Seung Soon Lee, MD; Phone Number: +82-33-240-5599; Email: hushh93@gmail.com
      • Contact: Ki Tae Suk, MD, PhD; Phone Number: +82-33-240-5826; Email: ktsuk@hallym.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

CRE- or VRE-rectal colonizer who have given written informed consent for fecal microbiota transplantation and collection of stool samples for CRE or VRE decolonization

Description

Inclusion Criteria:

• Patients over 19 years-old with carbapenem-resistant Enterobacteriaceae(CRE) or vancomycin-resistant Enterococci(VRE) rectal colonization
• Patients who have received written informed consent for fecal microbiota transplantation and collection of stool samples

Exclusion Criteria:

• Patients who have not completed acute-phase treatment, including antibiotic treatment
• If patients are pregnant, may be pregnant, or are lactating
• Patients who have not received written informed consent for the study enrollment
• Patients who are judged to be unhelpful to participate in the study according to the researcher's judgment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
carbapenem-resistant Enterobacteriaceae; FMT using frozen or capsulized stool	Other: fecal microbiota transplantation; frozen or capsulized stool from donors who had already finished recommended blood & stool screening for stool donors
vancomycin-resistant Enterococci; FMT using frozen or capsulized stool	Other: fecal microbiota transplantation; frozen or capsulized stool from donors who had already finished recommended blood & stool screening for stool donors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
successful decolonization of carbapenem-resistant Enterobacteriaceae or vancomycin-resistant Enterococci in the gut within 3 months after fecal microbiota transplantation	Successful decolonization of carbapenem-resistant Enterobacteriaceae or vancomycin-resistant Enterococci was defined as three consecutive, carbapenem-resistant Enterobacteriaceae or vancomycin-resistant Enterococci-negative surveillance rectal swab cultures repeated with a 3-day interval within 3 months after fecal microbiota transplantation	within 3 months

Collaborators and Investigators

• Sponsor: Chuncheon Sacred Heart Hospital
• Investigators: Principal Investigator: Seung Soon Lee, MD, Chuncheon Sacred Heart Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Estimated): August 31, 2023
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 27, 2020
• First Submitted That Met QC Criteria: October 4, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Carbapenem-Resistant Enterobacteriaceae; Vancomycin-Resistant Enterococci
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Enterobacteriaceae Infections
• Other Study ID Numbers: 2020-08-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No