Fecal Microbiota Transplantation (FMT) to Decolonize Antibiotic - Resistant Bacteria (ARB) - New Protocol

Study Overview
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Brief Summary
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The aim of the study is to assess the safety and efficacy of new protocol fecal microbiota transplantation (FMT) in the eradication of antibiotic resistant bacteria, including those featuring of resistance to new generation antibiotics. This study should answer the following research questions: Will new treatment protocol and fully anaerobic FMT be effective in decolonization of ARB? Will FMT improve the prognosis and quality of life in patients at high risk of ARB infection?

Detailed Description
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Fecal microbiota transplantation (FMT) was shown to be very efficient in treatment of relapsed and refractory Clostridium difficile infection and became a standard treatment. The investigators company produces and uses FMT not only in case of Clostridioides difficile colitis, but also in case of gut colonization with antibiotic-resistant bacteria and other indications as a clinical studies under Bioethical Committee approval. Company's flagship program to decolonize ARB is based on assumption that physiological gut flora may outcompete the pathogenic bacteria similarly as in case of Clostridium difficile and lead to loss of colonization. Patients colonized with ARB are characterized by poor diversity of gut microbiome (dysbiosis), which makes them vulnerable to further infections. In case of gut mucosa injury and severe immune suppression, these colonizing bacteria may cause severe systemic infections. During this interventional prospective, single arm, observational study, the investigators collect the information about the safety and effectiveness of FMT in gut decolonization with antibiotic-resistance bacteria (ARB) using their new treatment protocol and own full-spectrum, full-richness, full-viability anaerobic FMT. The project protocol is based on the intervention (fecal microbiota transplantation; FMT) in capsules (or colonoscopy if per os route is not possible) applied twice - on day 7th after procedure initiation and between day 9-14 within extended period, low dose (1/6th every day) application. All patient are premedicated with non-absorbable antibiotics on days 1-5 and a bowel cleansing on day 6 from the screening. After the end of the eradication procedure, the patient proceeds to the follow-up assessment stage and is observed up to 360 days with longitudinal samples collection.

Official Title
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Fecal Microbiota Transplantation to Eradicate Antibiotic-resistance Bacteria From the Gastrointestinal Tract of Patients at High Risk of Infection and/or to Cut Off the Spread of Bacteria With Dangerous Mechanisms of Antibiotic Resistance

Conditions
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Drug Resistance, Bacterial, Antimicrobial Drug Resistance

Intervention / Treatment
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* Procedure: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 6 months Population of patients colonized with antibiotic-resistant bacteria, as follows: strains of antibiotic-resistant bacteria that exhibit resistance mechanisms to carbapenems (MBL+: NDM+, VIM+ or others), KPC+, OXA-48+ or confirmed resistance to carbapenems without a specific genetic mechanism strains of Enterobacteriaceae resistant to beta lactams and other antibiotics in the case of multi-drug resistance (e.g. in the ESBL resistance mechanism and others) of the types including Escherichia, Enterobacter, Klebsiella, strains of P. aeruginosa, A. baumannii (together included in, among others, the ESKAPE group) Gram (+) enterococci E. faecalis or E. faecium or other bacteria resistant to vancomycin (VRE), linezolid and strains of S. aureus resistant to methicillin (MRSA) or vancomycin other multidrug-resistant or drug-resistant strains with threatening clinical resistance mechanisms or in patients vulnerable to infection with a particular pathogen Absolute neutrophil count in the peripheral blood up to 3 days before FMT > 500/ul (in the case of tandem multiple FMTs, in patients with an expected decrease in neutrophil values, the test should be repeated before each FMT when the timeframe between FMTs is longer than 3 days, and in patients without an expected decrease in the value of neutrophils below 500 cells/ul peripheral blood counts are valid for 28 days) Signing of the informed consent for participation in the study. Exclusion Criteria: Inability to obtain informed consent and lack of consent Blood neutrophil count <500/uL on the day of fecal microbiota transplantation or expected decrease to the mentioned number within 2 consecutive days Active infection requiring intensive antimicrobial treatment on FMT day or the first 7 days after FMT in immunocompetent patients (without immunosuppression or immunodeficiency) Clinical signs of mucositis 7 days prior to FMT Contraindications to FMT via upper and lower gastrointestinal tract (e.g. perforation of the digestive tract, rectal atresia, discontinuity of the digestive tract and others) Severe food allergy with the anaphylaxis history

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group, open label, observational study with intervention (Fecal Microbiota Transplantation)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>Antibiotics pre-treatment on days 1-5 and a bowel cleansing on day 6. Days 7-14 are dedicated to active eradication treatment with FMT. First dose on day 7 and second dose in days 9-14 (1/6 of full dose every day). | Procedure: Fecal Microbiota Transplantation<br>* Fecal Microbiota Transplantation in capsules or suspension obtained from healthy unrelated donor introduced two times per treatment: for capsules - FMT administration: day 7 (full dose) and days from 9 to 14 (prolonged intake regimen) for suspension - FMT administration: day 7 and day 14<br>* Other names: MBiotix HBI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication of gut colonizing antibiotic-resistant bacteria | The effectiveness of the therapy is assessed by means of rectal swabs and/or stool cultures after 30, 60, 90, 180 and 360 days (i.e. after a month, two, three and six) from the end of the eradication procedure | Baseline, 30, 60, 90, 180, 360 days after the end of eradication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in the diversity of the recipients' gut microbiota | Assesment of microbiome changes after treatment through a multi-omic analysis | from pre-treatment to 360 days after-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotic-resistant bacteria decolonization, Gastrointestinal tract colonization, Eradication procedure, Fecal Microbiota Transplantation