Fecal Microbiota Transplantation for CRE/VRE

Fecal Microbiota Transplantation for Eradication of Intestinal Colonization of Carbapenem-resistant Enterobacteriaceae and Vancomycin-resistant Enterococcus: a Pilot Study

Multidrug-resistant organisms (MDRO) present an increasingly serious public health threat to the global community.The prevalence of various MDRO, including carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococcus (VRE), has been increasing worldwide, and some have become endemic in certain countries. Data from the Hospital Authority showed that the number of carbapenemase- producing Enterobacteriaceae (CPE) cases increased from 36 in 2012 to 134 in 2015. A large outbreak of VRE involving >200 patients was recently reported in a tertiary hospital in Hong Kong.

The primary site of colonization and persistence of most MDRO is in the gastrointestinal tract. Carriage can persist for months, with up to 40% of individuals still having colonization one year after hospital discharge. Outbreaks of MDRO have been reported in hospitals and long-term care facilities. Around 10% of patients colonized with MDRO would develop clinical infections by the same organism. Infections caused by these MDRO carry significant morbidity and high mortality of up to 50%, however, there is no proven therapy for eradication of intestinal colonization of MDRO.

There is accumulating evidence showing that the gut microbiota plays an important role in the control of intestinal colonization and infection by pathogenic bacteria. Administration of obligate anaerobic commensal bacteria to mice has been shown to markedly reduce VRE colonization. Preliminary evidence, mainly from anecdotal reports, have shown that fecal microbiota transplantation (FMT) in human carriers of MDRO were safe and potentially effective in eliminating intestinal colonization by various MDRO, including CRE and VRE, even in immunocompromised patients. Therefore, investigators hypothesize that FMT will be safe and potentially effective in eradicating intestinal colonization of CRE and VRE.

This is a prospective pilot study to evaluate whether FMT is safe and effective to eradicate intestinal colonization of CRE and VRE.

Study Overview

• Status: Completed
• Conditions: Antimicrobial Resistance; Colonization
• Intervention / Treatment: Biological: FMT infusion

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For cases:

1. Age ≥18 years old

2. Two or more stool or rectal swab positive for CRE or VRE at least one week apart.

   [CRE is defined as presence of any Enterobacteriaceae with resistance to any of the carbapenems. VRE is defined as presence of Enterococcus species resistant to vancomycin.]

3. Not receiving antimicrobial therapy for at least 48 hours prior to infusion of FMT

For controls:

1. Age ≥18 years old
2. Two or more stool or rectal swab positive for CRE or VRE at least one week apart.
3. Not receiving antimicrobial therapy for at least 48 hours prior to infusion of FMT
4. Refuse to consent for FMT infusion but consent for other study procedures listed in the protocol.

Exclusion Criteria:

1. Active infection with CRE or VRE requiring antimicrobial therapy
2. Pregnancy
3. Active gastrointestinal tract infection or inflammatory disorders
4. Recent intra-abdominal surgery
5. Short gut syndrome
6. Use of medications which alter gastrointestinal motility at the time of inclusion
7. Post-allogeneic hematopoietic stem cell transplant patients with history of gastrointestinal tract graft versus host disease
8. Presence of intra-abdominal device which would increase risk of peritonitis
9. ANC <500/mm3
10. HIV infection with CD4 <200 cells/mm3
11. On chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT infusion; FMT will be performed using frozen donor stool samples obtained from the stool bank of CUHK. 100-200ml of FMT solution or sterile saline will be infused over 2-3 minutes into the distal duodenum or jejunum via OGD.	Biological: FMT infusion; Fecal microbiota transplantation via OGD
No Intervention: Control; No FMT infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal colonization of CRE/VRE	Absence of intestinal colonization of CRE/VRE	2 weeks to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence, severity and relatedness of adverse events	12 months post FMT
Intestinal microbiota	Changes in intestinal microbiota	Before and 12 months after FMT

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2018
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: March 25, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 7, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: FMT protocol v.2 10Oct2017

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