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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fecal Microbiota Transplantation | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal Microbiota Transplantation | Procedure | 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Infections-oriented safety profile assessment | Number of adverse events (AE) regarding infectious complications after FMT | During 3 months form FMT |
Inclusion Criteria:
Age > 6 months
Population of patients colonized with antibiotic-resistant bacteria, as follows:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jaroslaw Bilinski, MD, PhD | Contact | 884 299 668 | +48 | jaroslaw.bilinski@human-biome.com |
| Dorota Makarewicz, PhD | Contact | 884 299 668 | +48 | dorota.makarewicz@human-biome.com |
| Name | Affiliation | Role |
|---|---|---|
| Jaroslaw Bilinski, MD, PhD | Human Biome Institute S.A. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uniwersyteckie Centrum Kliniczne, Klinika Gastroenterologii i Hepatologii | Recruiting | Gdansk | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31662862 | Background | Rokkas T, Gisbert JP, Gasbarrini A, Hold GL, Tilg H, Malfertheiner P, Megraud F, O'Morain C. A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection. United European Gastroenterol J. 2019 Oct;7(8):1051-1063. doi: 10.1177/2050640619854587. Epub 2019 May 27. | |
| 29555994 |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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Single group, open label, observational study with intervention (Fecal Microbiota Transplantation)
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| Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii | Recruiting | Gdansk | Poland |
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| Uniwersyteckie Centrum Kliniczne, Klinika Pediatrii, Hematologii i Onkologii | Recruiting | Gdansk | Poland |
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| WOJEWÓDZKI SZPITAL ZESPOLONY W KIELCACH, Klinika Chorób Zakaźnych | Recruiting | Kielce | Poland |
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| WIM-PIB: Klinika Chorób Infekcyjnych i Alergologii, Klinika Gastroenterologii i Chorób Wewnętrznych | Recruiting | Warsaw | Poland |
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| 22726443 | Background | Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, Reading NC, Villablanca EJ, Wang S, Mora JR, Umesaki Y, Mathis D, Benoist C, Relman DA, Kasper DL. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012 Jun 22;149(7):1578-93. doi: 10.1016/j.cell.2012.04.037. |
| 24096337 | Background | Buffie CG, Pamer EG. Microbiota-mediated colonization resistance against intestinal pathogens. Nat Rev Immunol. 2013 Nov;13(11):790-801. doi: 10.1038/nri3535. Epub 2013 Oct 7. |
| 23334413 | Background | Diehl GE, Longman RS, Zhang JX, Breart B, Galan C, Cuesta A, Schwab SR, Littman DR. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature. 2013 Feb 7;494(7435):116-20. doi: 10.1038/nature11809. Epub 2013 Jan 13. |
| 28369341 | Background | Bilinski J, Grzesiowski P, Sorensen N, Madry K, Muszynski J, Robak K, Wroblewska M, Dzieciatkowski T, Dulny G, Dwilewicz-Trojaczek J, Wiktor-Jedrzejczak W, Basak GW. Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study. Clin Infect Dis. 2017 Aug 1;65(3):364-370. doi: 10.1093/cid/cix252. |
| 25982290 | Background | Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015 Jul;149(1):223-37. doi: 10.1053/j.gastro.2015.05.008. Epub 2015 May 15. |
| 25041704 | Background | Kronman MP, Zerr DM, Qin X, Englund J, Cornell C, Sanders JE, Myers J, Rayar J, Berry JE, Adler AL, Weissman SJ. Intestinal decontamination of multidrug-resistant Klebsiella pneumoniae after recurrent infections in an immunocompromised host. Diagn Microbiol Infect Dis. 2014 Sep;80(1):87-9. doi: 10.1016/j.diagmicrobio.2014.06.006. Epub 2014 Jun 21. |