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Qiao T, Wen XH. Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies. World J Gastroenterol 2025; 31:100827. [PMID: 39811502 PMCID: PMC11684203 DOI: 10.3748/wjg.v31.i2.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/30/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.
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Affiliation(s)
- Tong Qiao
- Department of Clinical Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Xian-Hui Wen
- College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China
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2
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Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis 2023; 77:S463-S470. [PMID: 38051967 DOI: 10.1093/cid/ciad644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.
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Affiliation(s)
- Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Miguel A. An overview of Clostridioides difficile and faecal microbiota transplant: implications for nursing practice. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2023; 32:546-549. [PMID: 37344135 DOI: 10.12968/bjon.2023.32.12.546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/23/2023]
Abstract
Clostridioides difficile bacteria can cause excessive diarrhoea in patients, leading to further complications, such as severe dehydration and sepsis. Although C.difficile bacteria tend to reside harmlessly in many people's bowels, prolonged antibiotic use can alter the bacterial balance of the bowel resulting in a C.difficile infection. Guidance from the National Institute for Health and Care Excellence recommends treating a C.difficile infection with further antibiotic therapy; however, it also states that in cases of recurrent infection, a faecal microbiota transplant (FMT) should be considered. This article focuses on the treatment modality of FMT and is aimed at increasing awareness of the treatment. As well as discussing how the nurse can approach the topic with a patient considering FMT, the article also considers the nurse's role throughout the process.
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Tetz G, Tetz V. Overcoming Antibiotic Resistance with Novel Paradigms of Antibiotic Selection. Microorganisms 2022; 10:2383. [PMID: 36557636 PMCID: PMC9781420 DOI: 10.3390/microorganisms10122383] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/04/2022] Open
Abstract
Conventional antimicrobial susceptibility tests, including phenotypic and genotypic methods, are insufficiently accurate and frequently fail to identify effective antibiotics. These methods predominantly select therapies based on the antibiotic response of only the lead bacterial pathogen within pure bacterial culture. However, this neglects the fact that, in the majority of human infections, the lead bacterial pathogens are present as a part of multispecies communities that modulate the response of these lead pathogens to antibiotics and that multiple pathogens can contribute to the infection simultaneously. This discrepancy is a major cause of the failure of antimicrobial susceptibility tests to detect antibiotics that are effective in vivo. This review article provides a comprehensive overview of the factors that are missed by conventional antimicrobial susceptibility tests and it explains how accounting for these methods can aid the development of novel diagnostic approaches.
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Affiliation(s)
- George Tetz
- Human Microbiology Institute, New York, NY 100141, USA
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Ramos RJ, Zhu C, Joseph DF, Thaker S, Lacomb JF, Markarian K, Lee HJ, Petrov JC, Monzur F, Buscaglia JM, Chawla A, Small-Harary L, Gathungu G, Morganstern JA, Yang J, Li J, Pamer EG, Robertson CE, Frank DN, Cross JR, Li E. Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases. MEDICAL RESEARCH ARCHIVES 2022; 10:10.18103/mra.v10i10.3318. [PMID: 36618438 PMCID: PMC9817289 DOI: 10.18103/mra.v10i10.3318] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions. AIM To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI). METHODS We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance. RESULTS The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels. CONCLUSION Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.
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Houf J. Faecal microbiota transplants: towards a healthy disgust scepticism. MEDICAL HUMANITIES 2021; 47:407-416. [PMID: 34509994 DOI: 10.1136/medhum-2020-012135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/05/2021] [Indexed: 06/13/2023]
Abstract
This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of 'truth' in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against 'toxins and diseases'. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust's role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against 'toxins and diseases'. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity-the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.
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Affiliation(s)
- Jessica Houf
- Communication and Media Studies, Louisiana Tech University, Ruston, LA 71272, USA
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Luz MRMPD, Waizbort RF. [Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature]. ACTA ACUST UNITED AC 2021; 27:859-878. [PMID: 33111793 DOI: 10.1590/s0104-59702020000400009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 06/04/2019] [Indexed: 01/05/2023]
Abstract
In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.
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FECAL MICROBIOTES TRANSPLANTATION TECHNOLOGIES: MEDICAL, BIOTECHNOLOGICAL AND REGULATORY ASPECTS. BIOTECHNOLOGIA ACTA 2021. [DOI: 10.15407/biotech14.01.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a treatment method based on donor's fecal solution injection into the patient's gastrointestinal tract. FMT is effectively used in the treatment of recurrent Clostridium difficile infection. There is also growing interest in the therapeutic application of the method to treat metabolic, autoimmune and other disorders that was not previously associated with intestinal microbiota. Despite the promising results of FMT use, the organizational and legal matters and that of the safety FMT application have not yet been resolved in the European and Ukrainian medical community. The purpose of this review was to summarize information on the FMT application and the regulatory aspects of its use. The analysis of the practical instructions provisions of for FMT applying in clinical practice was carried out, and the bioethical problems associated with the FMT use were investigated.
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Ramai D, Zakhia K, Fields PJ, Ofosu A, Patel G, Shahnazarian V, Lai JK, Dhaliwal A, Reddy M, Chang S. Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. Dig Dis Sci 2021; 66:369-380. [PMID: 32166622 DOI: 10.1007/s10620-020-06185-7] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/28/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules. AIM To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI. METHODS We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design. RESULTS Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%. CONCLUSION CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.
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Affiliation(s)
- Daryl Ramai
- Department of Medicine, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, 121 DeKalb Ave, Brooklyn, NY, 11201, USA.
| | - Karl Zakhia
- Department of Medicine, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, 121 DeKalb Ave, Brooklyn, NY, 11201, USA
| | - Paul J Fields
- School of Medicine, Windward Islands Research and Education Foundation, St. George's University, True Blue, Grenada
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, 121 DeKalb Ave, Brooklyn, NY, 11201, USA
| | - Goonja Patel
- School of Medicine, Windward Islands Research and Education Foundation, St. George's University, True Blue, Grenada
| | - Vahe Shahnazarian
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, 121 DeKalb Ave, Brooklyn, NY, 11201, USA
| | - Jonathan K Lai
- Department of Pathology, McGill University, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Grenada
| | - Amaninder Dhaliwal
- Division of Gastroenterology, University of Nebraska Medical Center, S 42nd and Emile St, Omaha, NE, 68198, USA
| | - Madhavi Reddy
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, 121 DeKalb Ave, Brooklyn, NY, 11201, USA
| | - Shannon Chang
- Division of Gastroenterology, NYU Langone Health, 40 East 38th Street, 23rd Floor, New York, NY, 10016, USA
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Gulati M, Singh SK, Corrie L, Kaur IP, Chandwani L. Delivery routes for faecal microbiota transplants: Available, anticipated and aspired. Pharmacol Res 2020; 159:104954. [DOI: 10.1016/j.phrs.2020.104954] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/11/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023]
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Sorbara MT, Littmann ER, Fontana E, Moody TU, Kohout CE, Gjonbalaj M, Eaton V, Seok R, Leiner IM, Pamer EG. Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity. Cell Host Microbe 2020; 28:134-146.e4. [PMID: 32492369 DOI: 10.1016/j.chom.2020.05.005] [Citation(s) in RCA: 266] [Impact Index Per Article: 53.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/11/2020] [Accepted: 05/06/2020] [Indexed: 02/03/2023]
Abstract
Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inter- and intra-species diversity in pathways that likely influence an isolate's ability to impact host health. These differences are likely to impact colonization resistance through lantibiotic expression or intestinal acidification, influence host mucosal immune cells and enterocytes via butyrate production, or contribute to synergism within a consortium by heterogenous polysaccharide metabolism. Identification of these specific functions could facilitate development of probiotic bacterial consortia that drive and/or restore in vivo microbiome functions.
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Affiliation(s)
- Matthew T Sorbara
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Infectious Diseases and Global Health, The University of Chicago, Chicago, IL 60637, USA.
| | - Eric R Littmann
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Emily Fontana
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Thomas U Moody
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Claire E Kohout
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Mergim Gjonbalaj
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vincent Eaton
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ruth Seok
- Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ingrid M Leiner
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA
| | - Eric G Pamer
- Duchossois Family Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Department of Medicine, Section of Infectious Diseases and Global Health, The University of Chicago, Chicago, IL 60637, USA.
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McCune V, Quraishi M, Manzoor S, Moran C, Banavathi K, Steed H, Massey D, Trafford G, Iqbal T, Hawkey P. Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection. EClinicalMedicine 2020; 20:100301. [PMID: 32300746 PMCID: PMC7152830 DOI: 10.1016/j.eclinm.2020.100301] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 02/05/2020] [Accepted: 02/19/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. METHODS Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. FINDINGS Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. INTERPRETATION The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.
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Affiliation(s)
- V.L. McCune
- Public Health England, Public Health Laboratory Birmingham, University Hospitals Birmingham NHS Foundation Trust, Heartlands Hospital, Bordesley Green East, Birmingham B5 9SS, England
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TH, England
- Microbiome Treatment Centre, IBR West Link Level 2, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, West Midlands B15 2TT, England
- Corresponding author.
| | - M.N. Quraishi
- Microbiome Treatment Centre, IBR West Link Level 2, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, West Midlands B15 2TT, England
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, England
| | - S. Manzoor
- Microbiome Treatment Centre, IBR West Link Level 2, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, West Midlands B15 2TT, England
| | - C.E. Moran
- Directorate of Infectious Diseases, University Hospitals Birmingham NHS Foundation Trust, Heartlands Hospital, Bordesley Green East, Birmingham B5 9SS, England
| | - K. Banavathi
- Department of Microbiology, University Hospitals of North Midlands, Stoke-on-Trent ST4 6QG, England
| | - H. Steed
- Department of Gastroenterology, The Royal Wolverhampton NHS Trust, New cross Hospital, Wolverhampton WV10 0QP, England
| | - D.C.O Massey
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, England
| | - G.R Trafford
- Department of Microbiology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX CV2 2 DX University Hospital, Clifford Bridge Road, Coventry CV2 2DX, England
| | - T.H. Iqbal
- Microbiome Treatment Centre, IBR West Link Level 2, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, West Midlands B15 2TT, England
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, England
| | - P.M. Hawkey
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TH, England
- Microbiome Treatment Centre, IBR West Link Level 2, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, West Midlands B15 2TT, England
- Department of Microbiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, England
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Kumar V, Fischer M. Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Expert Opin Biol Ther 2020; 20:73-81. [PMID: 31690143 DOI: 10.1080/14712598.2020.1689952] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.
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Affiliation(s)
- Vinod Kumar
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Monika Fischer
- Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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14
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Tamilarasan AG, Irving P, Meadows CI, Goldenberg S. Faecal microbiota transplantation for refractory C lostridium difficile infection. BMJ Case Rep 2019; 12:12/11/e231027. [PMID: 31780599 DOI: 10.1136/bcr-2019-231027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.
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Affiliation(s)
| | - Peter Irving
- Department of Gastroenterology, Guy's and St Thomas' Hospitals, London, UK
| | - Christopher Is Meadows
- Department of Critical Care, Guy's and St Thomas' Hospitals, London, UK.,Faculty of Life Sciences and Medicine, King's College London, London, London, UK
| | - Simon Goldenberg
- Centre for Clinical Infection and Diagnostics Research, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Hocquart M, Pham T, Kuete E, Tomei E, Lagier JC, Raoult D. Successful Fecal Microbiota Transplantation in a Patient Suffering From Irritable Bowel Syndrome and Recurrent Urinary Tract Infections. Open Forum Infect Dis 2019; 6:ofz398. [PMID: 31660360 DOI: 10.1093/ofid/ofz398] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 09/26/2019] [Indexed: 12/22/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder affecting 9%-23% of the population across the world. The relative efficacy of fecal microbiota transplantation (FMT) on IBS symptoms was demonstrated in a double-blind, randomized study. Methods We describe the case of a 73-year-old woman suffering from IBS (abdominal pain, bloating, and abundant and disabling diarrhea, with 10-15 stools a day) and repetitive urinary tract infection (UTI; 5 episodes in 6 months, including 3 the last 2 months) for several years, generating an impaired quality of life. She received an FMT with 400 mL of fecal infusion from a healthy donor via a nasogastric tube after bowel lavage. Her digestive microbiota was analyzed using culturomic and metagenomic targeting 16S rRNA sequencing methods. Results Eight months after transplantation, we observed a significant reduction in frequency and improvement in stool consistency (3-4 molded stools a day against 10-15 before the transplant) and no recurrence of urinary infection (as previously reported). Using culturomics, we found 12 bacteria present in the fecal infusion and post-transplant stool; these were absent pretransplant. Three of them (Intestinimonas massiliensis, Oscillibacter massiliensis, and Provencibacter massiliensis) were previously discovered and cultivated in our laboratory using culturomics. Using metagenomics, we also observed 12 bacteria, different from those observed during culture, that could have been transferred to the patient by FMT. Conclusions In this case report, IBS symptoms and UTI frequency decreased after FMT UTI. Further studies involving more patients would be relevant to confirm this work and develop bacteriotherapy.
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Affiliation(s)
- Marie Hocquart
- Aix Marseille Univ, IRD, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Thao Pham
- Aix Marseille Univ, IRD, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Edmond Kuete
- Aix Marseille Univ, IRD, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Enora Tomei
- IHU-Méditerranée Infection, Marseille, France.,Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France
| | - Jean Christophe Lagier
- Aix Marseille Univ, IRD, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Didier Raoult
- Aix Marseille Univ, IRD, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
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16
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Mullish BH, Quraishi MN, Segal JP, McCune VL, Baxter M, Marsden GL, Moore D, Colville A, Bhala N, Iqbal TH, Settle C, Kontkowski G, Hart AL, Hawkey PM, Williams HR, Goldenberg SD. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. J Hosp Infect 2019; 100 Suppl 1:S1-S31. [PMID: 30173851 DOI: 10.1016/j.jhin.2018.07.037] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 07/23/2018] [Indexed: 02/08/2023]
Affiliation(s)
- Benjamin H Mullish
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, Paddington, London, UK
| | - Mohammed Nabil Quraishi
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jonathan P Segal
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Inflammatory Bowel Disease Unit, St Mark's Hospital, Harrow, London, UK
| | - Victoria L McCune
- Public Health England, Public Health Laboratory Birmingham, Birmingham, UK; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | - Melissa Baxter
- Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | | | - David Moore
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Alaric Colville
- Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Neeraj Bhala
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Applied Health Research, University of Birmingham, Birmingham, UK; Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK
| | - Tariq H Iqbal
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK
| | - Christopher Settle
- Department of Microbiology, City Hospitals Sunderland NHS Foundation Trust, Sunderland, UK
| | | | - Ailsa L Hart
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Inflammatory Bowel Disease Unit, St Mark's Hospital, Harrow, London, UK
| | - Peter M Hawkey
- Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | - Horace Rt Williams
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, Paddington, London, UK
| | - Simon D Goldenberg
- Centre for Clinical Infection and Diagnostics Research, King's College London, London, UK; Department of Microbiology, Guy's and St Thomas' NHS Foundation Trust, London UK.
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17
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Schepici G, Silvestro S, Bramanti P, Mazzon E. The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials. Cell Transplant 2019; 28:1507-1527. [PMID: 31512505 PMCID: PMC6923550 DOI: 10.1177/0963689719873890] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and
degenerative disease that affects the central nervous system. A recent study
showed that interaction between the immune system and the gut microbiota plays a
crucial role in the development of MS. This review reports the clinical studies
carried out in recent years that aimed to evaluate the composition of the
microbiota in patients with relapsing–remitting MS (RR-MS). We also report what
is available in the literature regarding the effectiveness of fecal microbiota
transplantation and the role of the diet in restoring the intestinal bacterial
population. Studies report that patients with RR-MS have a microbiota that,
compared with healthy controls, has higher amounts of
Pedobacteria, Flavobacterium,
Pseudomonas, Mycoplana,
Acinetobacter, Eggerthella,
Dorea, Blautia,
Streptococcus and Akkermansia. In
contrast, MS patients have a microbiota with impoverished microbial populations
of Prevotella, Bacteroides,
Parabacteroides, Haemophilus,
Sutterella, Adlercreutzia,
Coprobacillus, Lactobacillus,
Clostridium, Anaerostipes and
Faecalibacterium. In conclusion, the restoration of the
microbial population in patients with RR-MS appears to reduce inflammatory
events and the reactivation of the immune system.
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Affiliation(s)
- Giovanni Schepici
- IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.,Both the authors contributed equally to this article
| | - Serena Silvestro
- IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.,Both the authors contributed equally to this article
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18
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Chen CC, Chen YN, Liou JM, Wu MS. From germ theory to germ therapy. Kaohsiung J Med Sci 2019; 35:73-82. [DOI: 10.1002/kjm2.12011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 11/22/2018] [Indexed: 12/16/2022] Open
Affiliation(s)
- Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Yen-Nien Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
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19
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Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis. FEMS Microbiol Lett 2019; 366:5304978. [DOI: 10.1093/femsle/fnz025] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 01/30/2019] [Indexed: 12/14/2022] Open
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20
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Ramai D, Zakhia K, Ofosu A, Ofori E, Reddy M. Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness. Ann Gastroenterol 2019; 32:30-38. [PMID: 30598589 PMCID: PMC6302197 DOI: 10.20524/aog.2018.0328] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 10/08/2018] [Indexed: 12/15/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has evolved into a robust and efficient means for treating recurrent Clostridium difficile infection (CDI). Our narrative review looks at the donor selection, preparation, delivery techniques and cost-effectiveness of FMT. We searched electronic databases, including PubMed, MEDLINE, Google Scholar, and Cochrane Databases, for studies that compared the biological effects of donor selection, fresh or frozen fecal preparation, and various delivery techniques. We also evaluated the cost-effectiveness and manually searched references to identify additional relevant studies. Overall, there is a paucity of studies that directly compare outcomes associated with related and non-related stool donors. However, inferences from prior studies indicate that the success of FMT does not depend on the donor-patient relationship. Over time, the use of unrelated donors has increased because of the formation of stool banks and the need to save processing time and capital. However, longitudinal studies are needed to clarify the optimal freezing time before microbial function declines. Several FMT techniques have been developed, such as colonoscopy, enema, nasogastric or nasojejunal tubes, and capsules. The comparable and high efficacy of FMT capsules, combined with their convenience, safety and aesthetically tolerable mode of delivery, makes it an attractive option for many patients. Cost-effective models comparing these various approaches support the use of FMT via colonoscopy as being the best strategy for the treatment of recurrent CDI.
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Affiliation(s)
- Daryl Ramai
- Department of Medicine, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn (Daryl Ramai)
| | - Karl Zakhia
- Department of Medicine, Elmhurst Medical Center, Queens (Karl Zakhia)
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn (Andrew Ofosu, Emmanuel Ofori, Madhavi Reddy), New York, USA
| | - Emmanuel Ofori
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn (Andrew Ofosu, Emmanuel Ofori, Madhavi Reddy), New York, USA
| | - Madhavi Reddy
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn (Andrew Ofosu, Emmanuel Ofori, Madhavi Reddy), New York, USA
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21
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Mullish BH, Quraishi MN, Segal JP, McCune VL, Baxter M, Marsden GL, Moore DJ, Colville A, Bhala N, Iqbal TH, Settle C, Kontkowski G, Hart AL, Hawkey PM, Goldenberg SD, Williams HRT. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut 2018; 67:1920-1941. [PMID: 30154172 DOI: 10.1136/gutjnl-2018-316818] [Citation(s) in RCA: 233] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 06/27/2018] [Accepted: 07/01/2018] [Indexed: 12/16/2022]
Abstract
Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.
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Affiliation(s)
- Benjamin H Mullish
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Mohammed Nabil Quraishi
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jonathan P Segal
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK
| | - Victoria L McCune
- Public Health England, Public Health Laboratory Birmingham, Birmingham, UK.,Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | - Melissa Baxter
- Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | | | - David J Moore
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Alaric Colville
- Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Neeraj Bhala
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Institute of Applied Health Research, University of Birmingham, Birmingham, UK.,Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - Tariq H Iqbal
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - Christopher Settle
- Department of Microbiology, City Hospitals Sunderland NHS Foundation Trust, Sunderland, Sunderland, UK
| | | | - Ailsa L Hart
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK
| | - Peter M Hawkey
- Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | - Simon D Goldenberg
- Centre for Clinical Infection and Diagnostics Research, King's College London, London, UK.,Department of Microbiology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Horace R T Williams
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
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22
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Process and Outcome of Fecal Microbiota Transplants in Patients With Recurrent Clostridium difficile Infection: A Prospective Study. Gastroenterol Nurs 2018; 40:411-419. [PMID: 28957971 DOI: 10.1097/sga.0000000000000233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
The incidence of Clostridium difficile infection is on the rise worldwide, causing high mortality rates and costing patients, hospitals, and insurance companies millions of dollars annually. Fecal microbiota transplants successfully treat recurrent C. difficile infections unresponsive to standard pharmacologic treatment such as flagyl, vancomycin, or rifaximin. Evidence in the literature provided the foundation for the development and refinement of this fecal microbiota transplant protocol. During the initial phase of the project, the protocol included patient selection criteria, donor screening/selection, infection control, fecal processing and delivery, and patient pre and postprocedure education. This article highlights the second phase of prospective testing of a nurse-driven protocol to implement fecal microbiota transplantation in patients with recurrent C. difficile infection. All stages of the protocol are explained as well as rationale for component parts to achieve successful patient outcomes when the protocol is carefully followed.
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23
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Shogbesan O, Poudel DR, Victor S, Jehangir A, Fadahunsi O, Shogbesan G, Donato A. A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients. Can J Gastroenterol Hepatol 2018; 2018:1394379. [PMID: 30246002 PMCID: PMC6139215 DOI: 10.1155/2018/1394379] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 08/06/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
Background Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown. Methods We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated. Results Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations. Conclusion We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.
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Affiliation(s)
- Oluwaseun Shogbesan
- Department of Medicine, Tower Health System, Sixth Avenue and Spruce Street, West Reading, PA 19611, USA
| | - Dilli Ram Poudel
- Hospitalist Services, Tower Health System, Sixth Avenue and Spruce Street, West Reading, PA 19611, USA
| | - Samjeris Victor
- Department of Biochemistry & Molecular Biology, Pennsylvania State University, State College, PA 16801, USA
| | - Asad Jehangir
- Hospitalist Services, Tower Health System, Sixth Avenue and Spruce Street, West Reading, PA 19611, USA
| | - Opeyemi Fadahunsi
- Division of Cardiology, Dalhousie University, Halifax, NS B3H 4RS, Canada
| | - Gbenga Shogbesan
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, Athens, GA 30606, USA
| | - Anthony Donato
- Department of Medicine, Tower Health System, Sixth Avenue and Spruce Street, West Reading, PA 19611, USA
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24
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A Retrospective Study Analyzing the Appropriateness of Initial Treatment of Clostridium difficile in Patients with Active Malignancy. Gastroenterol Res Pract 2018; 2018:7192728. [PMID: 29991944 PMCID: PMC5994314 DOI: 10.1155/2018/7192728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 04/19/2018] [Indexed: 01/05/2023] Open
Abstract
Background Clostridium difficile infection (CDI) is the leading cause of hospital-associated gastrointestinal illness. Previous studies reported that patients with active malignancy are at high risk for CDIs, and yet they are still classified as nonsevere CDI and initially treated with metronidazole. Our aim is to investigate the need for the escalation of antibiotic therapy in patients with CDI and active cancer treated with oral metronidazole versus oral vancomycin. Methods This is a retrospective study of adult patients admitted with CDI and any underlying active malignancy at Beaumont Hospital, Royal Oak, Michigan, from January 2008 to December 2014. Inclusion criteria included age > 18 years old, polymerase chain reaction- (PCR-) proven CDI, and active malignancy. Results 197 patients were included in the final analysis. 44.8% of the metronidazole group required escalation of therapy compared to 15.2% in the vancomycin group (p value = 0.001). 29.8% of the combination group (metronidazole and vancomycin) underwent deescalation of antibiotics, which was significantly higher compared to 2.2% of patients in the vancomycin group (p value < 0.001). Discussion Our results support the initial use of vancomycin or a combination (metronidazole and vancomycin) versus metronidazole in patients with CDI and active malignancy.
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25
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Goldenberg SD, Batra R, Beales I, Digby-Bell JL, Irving PM, Kellingray L, Narbad A, Franslem-Elumogo N. Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review. Infect Dis Ther 2018; 7:71-86. [PMID: 29450831 PMCID: PMC5840108 DOI: 10.1007/s40121-018-0189-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Indexed: 12/13/2022] Open
Abstract
Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a 'normal' microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this 'ultimate probiotic' is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the 'active ingredient' of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.
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Affiliation(s)
- Simon D Goldenberg
- Centre for Clinical Infection and Diagnostics Research (CIDR), King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, UK.
| | - Rahul Batra
- Centre for Clinical Infection and Diagnostics Research (CIDR), King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Ian Beales
- Department of Gastroenterology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
| | | | - Peter Miles Irving
- Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Lee Kellingray
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Arjan Narbad
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Ngozi Franslem-Elumogo
- Department of Medical Microbiology, Eastern Pathology Alliance, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
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26
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Hopkins RJ, Wilson RB. Treatment of recurrent Clostridium difficile colitis: a narrative review. Gastroenterol Rep (Oxf) 2018; 6:21-28. [PMID: 29479439 PMCID: PMC5806400 DOI: 10.1093/gastro/gox041] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 10/17/2017] [Accepted: 10/31/2017] [Indexed: 12/11/2022] Open
Abstract
Clostridium difficile is a gram-positive, spore-forming, obligate anaerobic bacillus that was originally isolated from the stool of a healthy neonate in 1935. In high-income countries, C. difficile is the most common cause of infectious diarrhoea in hospitalized patients. The incidence of C. difficile infection in the USA has increased markedly since 2000, with hospitalizations for C. difficile infections in non-pregnant adults doubling between 2000 and 2010. Between 20% and 35% of patients with C. difficile infection will fail initial antibiotic treatment and, of these, 40-60% will have a second recurrence. Recurrence of C. difficile infection after initial treatment causes substantial morbidity and is a major burden on health care systems. In this article, current treatments for recurrent C. difficile infection are reviewed and future directions explored. These include the use of antibiotics, probiotics, donor faecal transplants, anion resins, secondary bile acids or anti-toxin antibodies.
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Affiliation(s)
- Roy J Hopkins
- Department of Upper GI Surgery, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Robert B Wilson
- Department of Upper GI Surgery, Liverpool Hospital, Sydney, New South Wales, Australia
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Jalanka J, Hillamaa A, Satokari R, Mattila E, Anttila VJ, Arkkila P. The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2018; 47:371-379. [PMID: 29226561 DOI: 10.1111/apt.14443] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 10/02/2017] [Accepted: 11/07/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects. AIM To analyse the long-term effect of FMT treatment in patients with recurrent C. difficile infection and to compare the outcome to antibiotic treated patients. METHODS Altogether 84 patients of which 45 received a FMT treatment and 39 served as controls receiving antibiotics for the infection were followed on average for 3.8 years. Their recovery and medical status was evaluated using a retrospective questionnaire, determining their quality of life, gastrointestinal symptoms and new diseases potentially related to the FMT. RESULTS There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options. CONCLUSION Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment.
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Affiliation(s)
- J Jalanka
- Immunobiology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - A Hillamaa
- Departments of Gastroenterology and Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
| | - R Satokari
- Immunobiology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - E Mattila
- Departments of Gastroenterology and Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
| | - V-J Anttila
- Departments of Gastroenterology and Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
| | - P Arkkila
- Departments of Gastroenterology and Infectious Diseases, Helsinki University Hospital, Helsinki, Finland
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Mintz M, Khair S, Grewal S, LaComb JF, Park J, Channer B, Rajapakse R, Bucobo JC, Buscaglia JM, Monzur F, Chawla A, Yang J, Robertson CE, Frank DN, Li E. Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis. PLoS One 2018; 13:e0190997. [PMID: 29385143 PMCID: PMC5791968 DOI: 10.1371/journal.pone.0190997] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 12/22/2017] [Indexed: 12/14/2022] Open
Abstract
Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.
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Affiliation(s)
- Michael Mintz
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Shanawaj Khair
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Suman Grewal
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Joseph F. LaComb
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Jiyhe Park
- Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, United States of America
| | - Breana Channer
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Ramona Rajapakse
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Juan Carlos Bucobo
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Jonathan M. Buscaglia
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Farah Monzur
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Anupama Chawla
- Department of Pediatrics, Stony Brook University, Stony Brook, New York, United States of America
| | - Jie Yang
- Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, New York, United States of America
| | - Charlie E. Robertson
- Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America
| | - Daniel N. Frank
- Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America
| | - Ellen Li
- Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America
- * E-mail:
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Zamudio-Tiburcio Á, Bermúdez-Ruiz H, Lezama-Guzmán HR, Guevara-Ortigoza MDP, Islas-Solares E, Sosa-López FA. Rompiendo paradigmas. Trasplante de microbiota intestinal: reporte preliminar. CIR CIR 2017; 85 Suppl 1:6-12. [DOI: 10.1016/j.circir.2016.11.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 11/26/2016] [Indexed: 02/07/2023]
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Resultados de la implementación de un programa multidisciplinar de trasplante de microbiota fecal por colonoscopia para el tratamiento de la infección recurrente por Clostridium difficile. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 40:605-614. [DOI: 10.1016/j.gastrohep.2017.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 02/22/2017] [Accepted: 03/13/2017] [Indexed: 12/16/2022]
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Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma N, Iqbal TH. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther 2017; 46:479-493. [PMID: 28707337 DOI: 10.1111/apt.14201] [Citation(s) in RCA: 428] [Impact Index Per Article: 53.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 08/16/2016] [Accepted: 06/01/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use. AIM To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation. METHODS A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data. RESULTS Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. CONCLUSION Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.
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Affiliation(s)
- M N Quraishi
- Department of Gastroenterology, University Hospital Birmingham, Birmingham, UK
| | - M Widlak
- Department of Gastroenterology, University Hospital Coventry and Warwickshire, Conventry, UK
| | - N Bhala
- Department of Gastroenterology, University Hospital Birmingham, Birmingham, UK.,Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK.,Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK
| | - D Moore
- Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK
| | - M Price
- Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK
| | - N Sharma
- Department of Gastroenterology, University Hospital Birmingham, Birmingham, UK.,Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK
| | - T H Iqbal
- Department of Gastroenterology, University Hospital Birmingham, Birmingham, UK.,Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK
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Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection: A meta-analysis? Diagn Microbiol Infect Dis 2017; 88:322-329. [DOI: 10.1016/j.diagmicrobio.2017.05.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 11/07/2016] [Accepted: 05/14/2017] [Indexed: 02/07/2023]
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Lan N, Ashburn J, Shen B. Fecal microbiota transplantation for Clostridium difficile infection in patients with ileal pouches. Gastroenterol Rep (Oxf) 2017; 5:200-207. [PMID: 28852524 PMCID: PMC5554389 DOI: 10.1093/gastro/gox018] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 02/02/2017] [Accepted: 02/20/2017] [Indexed: 12/30/2022] Open
Abstract
Background:Clostridium difficile infection (CDI) in patients with ileal pouch-anal anastomosis (IPAA) has been increasingly recognized. The aim of this study was to evaluate the outcome of fecal microbiota transplantation (FMT) in patients with pouch and CDI. Methods: All consecutive patients that underwent FMT for CDI from 2012 to 2016 were extracted from our IRB-approved, prospectively maintained Registry of Pouch Disorders. The primary outcome was negative stool tests for Clostridium difficile after FMT and the secondary outcomes were symptomatic and endoscopic responses. Results: A total of 13 patients were included in this study, with 10 being Caucasian males (76.9%). All patients had underlying ulcerative colitis for J pouch surgery. After a mean of 2.8±0.8 courses of antibiotic treatments was given and failed, 22 sessions of FMT were administered with an average of 1.7±1.1 sessions each. Within the 22 sessions, 16 were given via pouchoscopy, 4 via esophagogastroduodenoscopy and 2 via enemas. All patients tested negative on C. difficile polymerase chain reaction (PCR) after the initial FMT with a total of 7/12 (58.3%) documented patients showed symptomatic improvements and 3/11 (27.3%) patients showed endoscopic improvement according to the modified Pouchitis Disease Activity Index. During the follow-up of 1.2±1.1 years, there were a total of five patients (38.5%) that had recurrence after the successful initial treatment and four of them were successfully treated again with FMT. Conclusions: FMT appeared to be effective in eradication of CDI in patients with ileal pouches. However, FMT had a modest impact on endoscopic inflammation and recurrence after FMT and recurrence was common.
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Affiliation(s)
- Nan Lan
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Jean Ashburn
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Bo Shen
- Center for Inflammatory Bowel Diseases, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA
- Corresponding author. The Interventional Inflammatory Bowel Disease (i-IBD) Unit, Digestive Disease and Surgery Institute-A31, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA. Tel: +1–216–444–9252; Fax: +1–216–444–6305;
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Abstract
Unrelated spore-forming bacteria share unique characteristics stemming from the presence of highly resistant endospores, leading to similar challenges in health and disease. These characteristics are related to the presence of these highly transmissible spores, which are commonly spread within the environment and are implicated in host-to-host transmission. In humans, spore-forming bacteria contribute to a variety of pathological processes that share similar characteristics, including persistence, chronicity, relapses and the maintenance of the resistome. We first outline the necessity of characterizing the totality of the spore-forming bacteria as the sporobiota based on their unique common characteristics. We further propose that the collection of all genes of spore-forming bacteria be known as the sporobiome. Such differentiation is critical for exploring the cross-talk between the sporobiota and other members of the gut microbiota, and will allow for a better understanding of the implications of the sporobiota and sporobiome in a variety of pathologies and the spread of antibiotic resistance.
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Affiliation(s)
- George Tetz
- Human Microbiology Institute, 423 West 127 Street, New York, NY 10027 USA
| | - Victor Tetz
- Human Microbiology Institute, 423 West 127 Street, New York, NY 10027 USA
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35
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van Beurden YH, Nieuwdorp M, van de Berg PJEJ, Mulder CJJ, Goorhuis A. Current challenges in the treatment of severe Clostridium difficile infection: early treatment potential of fecal microbiota transplantation. Therap Adv Gastroenterol 2017; 10:373-381. [PMID: 28491142 PMCID: PMC5405882 DOI: 10.1177/1756283x17690480] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a very effective treatment for recurrent Clostridium difficile infection (CDI). Less is known about the application of FMT as a curative treatment of severe or complicated CDI. In this review, we present and discuss evidence supporting the curative use of FMT in severe or complicated CDI. We performed a literature search in PubMed and Embase for studies on the curative use of FMT in severe or complicated CDI. In addition, we describe a patient with severe CDI not responding to initial antibiotic treatment, who was successfully treated with curative FMT. We found 23 reports (12 case reports; 11 case series) about FMT as treatment for severe or complicated CDI. The patients described all had severe or complicated CDI, did not respond to conventional CDI antibiotic treatment and received FMT as last resort treatment. Patients were treated with (sequential) FMT, whether or not followed by additional antibiotic treatment for CDI. FMT, with or without additional antibiotic CDI treatment, appears to be a promising curative treatment option in patients with severe and complicated CDI, or only complicated CDI, who do not respond sufficiently to conventional antibiotic treatment. Treatment with FMT should be considered in these patients before proceeding to emergency bowel surgery.
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Affiliation(s)
| | - Max Nieuwdorp
- Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Chris J. J. Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Abraham Goorhuis
- Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Garg N, Luzzatto-Knaan T, Melnik AV, Caraballo-Rodríguez AM, Floros DJ, Petras D, Gregor R, Dorrestein PC, Phelan VV. Natural products as mediators of disease. Nat Prod Rep 2017; 34:194-219. [PMID: 27874907 PMCID: PMC5299058 DOI: 10.1039/c6np00063k] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Covering: up to 2016Humans are walking microbial ecosystems, each harboring a complex microbiome with the genetic potential to produce a vast array of natural products. Recent sequencing data suggest that our microbial inhabitants are critical for maintaining overall health. Shifts in microbial communities have been correlated to a number of diseases including infections, inflammation, cancer, and neurological disorders. Some of these clinically and diagnostically relevant phenotypes are a result of the presence of small molecules, yet we know remarkably little about their contributions to the health of individuals. Here, we review microbe-derived natural products as mediators of human disease.
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Affiliation(s)
- Neha Garg
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
| | - Tal Luzzatto-Knaan
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
| | - Alexey V. Melnik
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
| | | | - Dimitrios J. Floros
- Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093
| | - Daniel Petras
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
| | - Rachel Gregor
- Department of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be’er Sheva 84105, Israel
| | - Pieter C. Dorrestein
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
| | - Vanessa V. Phelan
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, CO 80045
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Baro E, Galperine T, Denies F, Lannoy D, Lenne X, Odou P, Guery B, Dervaux B. Cost-Effectiveness Analysis of Five Competing Strategies for the Management of Multiple Recurrent Community-Onset Clostridium difficile Infection in France. PLoS One 2017; 12:e0170258. [PMID: 28103289 PMCID: PMC5245822 DOI: 10.1371/journal.pone.0170258] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 12/31/2016] [Indexed: 12/17/2022] Open
Abstract
Background Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France. Methods We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses. Results Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY. Conclusions FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY.
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Affiliation(s)
- Emilie Baro
- Univ. Lille, CHU Lille, EA 2694 - Santé Publique: Epidémiologie et Qualité des Soins, Lille, France
- * E-mail:
| | - Tatiana Galperine
- CHU Lille, Maladies Infectieuses, French Group of Faecal Microbiota Transplantation (GFTF), Lille, France
| | - Fanette Denies
- CHU Lille, Direction de la Recherche en Santé, Lille, France
| | - Damien Lannoy
- Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille, France
| | - Xavier Lenne
- CHU Lille, Département d’Information Médicale, Lille, France
| | - Pascal Odou
- Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille, France
| | - Benoit Guery
- CHU Lille, Maladies Infectieuses, French Group of Faecal Microbiota Transplantation (GFTF), Lille, France
- Univ. Lille, CHU Lille, EA 7366 - Recherche Translationnelle: Relations Hôte-Pathogènes, Lille, France
| | - Benoit Dervaux
- Univ. Lille, CHU Lille, EA 2694 - Santé Publique: Epidémiologie et Qualité des Soins, Lille, France
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Kim S, Lee Y, Kim SH. Safety and effectiveness of fecal microbiota transplantation: a systematic review. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2017. [DOI: 10.5124/jkma.2017.60.9.761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Soyoung Kim
- Division for New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Yeowool Lee
- Division for New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Seok-Hyun Kim
- Division for New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
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The Use and Efficacy of Fecal Microbiota Transplantation for Refractory Clostridium difficile in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2704-2710. [PMID: 27755271 DOI: 10.1097/mib.0000000000000950] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Clostridium difficile (CD) is an anaerobic, spore-forming bacillus that is responsible for a spectrum of gastrointestinal illness ranging from asymptomatic carriage to toxic megacolon and death. The prevalence of CD infection is increasing in both hospitalized and community-based inflammatory bowel disease populations. Standard antibiotic therapy fails to cure or prevent recurrence in more than 50% of patients, thus increasing the need for alternative therapies. Recently, fecal microbiota transplantation has received renewed attention as a therapy for refractory or recurrent CD infection. A high success rate combined with a favorable safety profile makes this therapy an attractive option for patients who have failed standard antibiotic therapy. Increasingly, this therapy is used in patients with CD infection and inflammatory bowel disease, as the combination of active inflammation and toxin-producing CD provides a challenging mix for clinicians.
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40
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Bradburne C, Hamosh A. Integrating the microbiome into precision medicine. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2016. [DOI: 10.1080/23808993.2016.1259562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Christopher Bradburne
- National Security Systems Biology Center, Asymmetric Operations Sector, Applied Physics Laboratory, Johns Hopkins University, Laurel, MD, USA
- McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Ada Hamosh
- McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA
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Abstract
GOALS We evaluated a cohort of patients referred to our center for presumed recurrent Clostridium difficile infection (CDI) to determine final diagnoses and outcomes. BACKGROUND As rates of CDI have increased, more patients are diagnosed with recurrent CDI and other sequelae of the infection. Distinguishing symptomatic patients with CDI from those who are colonized with an alternative etiology of diarrheal symptoms may be challenging. MATERIALS AND METHODS We performed a retrospective review of 117 patients referred to our center for recurrent CDI between January 2013 and June 2014. Data collected included demographics, the referring provider, previous anti-CDI treatment, and significant medical conditions. In addition, we gathered data on atypical features of CDI and investigations obtained to investigate the etiology of symptoms. Outcomes included rates of alternative diagnoses and the accuracy of CDI diagnosis by the referral source. RESULTS The mean age was 61 years, and 70% were female. About 29 patients (25%) were determined to have a non-CDI diagnosis. Most common alternative diagnoses included irritable bowel syndrome (18 patients: 62%) and inflammatory bowel disease (3 patients:10%). The age was inversely correlated with the rate of non-CDI diagnosis (P=0.016). Of the remaining 88 (75%) patients with a confirmed diagnosis of CDI, 25 (28%) received medical therapy alone and 63 (72%) underwent fecal microbiota transplantation. CONCLUSIONS Among patients referred to our center for recurrent CDI, a considerable percentage did not have CDI, but rather an alternative diagnosis, most commonly irritable bowel syndrome. The rate of alternative diagnosis correlated inversely with age. Providers should consider other etiologies of diarrhea in patients presenting with features atypical of recurrent CDI.
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Fecal microbiota transplant in patients with Clostridium difficile infection. J Trauma Acute Care Surg 2016; 81:756-64. [DOI: 10.1097/ta.0000000000001195] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Abstract
Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component. Fecal transfers are increasingly common in animal models and humans. This essay notes that bacteria may not be the only player in donor feces that can affect the recipient's biology.
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Affiliation(s)
- Diana P. Bojanova
- Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Seth R. Bordenstein
- Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America
- * E-mail:
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Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection: A Multicenter Experience. J Clin Gastroenterol 2016; 50:398-402. [PMID: 26125460 DOI: 10.1097/mcg.0000000000000374] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
GOAL Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI). BACKGROUND FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated. STUDY METHODS A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms. RESULTS A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (≤90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (≥90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred. CONCLUSIONS FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.
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Woloszynek S, Pastor S, Mell JC, Nandi N, Sokhansanj B, Rosen GL. Engineering Human Microbiota: Influencing Cellular and Community Dynamics for Therapeutic Applications. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2016; 324:67-124. [PMID: 27017007 DOI: 10.1016/bs.ircmb.2016.01.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The complex relationship between microbiota, human physiology, and environmental perturbations has become a major research focus, particularly with the arrival of culture-free and high-throughput approaches for studying the microbiome. Early enthusiasm has come from results that are largely correlative, but the correlative phase of microbiome research has assisted in defining the key questions of how these microbiota interact with their host. An emerging repertoire for engineering the microbiome places current research on a more experimentally grounded footing. We present a detailed look at the interplay between microbiota and host and how these interactions can be exploited. A particular emphasis is placed on unstable microbial communities, or dysbiosis, and strategies to reestablish stability in these microbial ecosystems. These include manipulation of intermicrobial communication, development of designer probiotics, fecal microbiota transplantation, and synthetic biology.
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Affiliation(s)
- S Woloszynek
- Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, United States of America
| | - S Pastor
- Department of Biomedical Engineering, Drexel University, Philadelphia, PA, United States of America
| | - J C Mell
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States of America
| | - N Nandi
- Division of Gastroenterology, Drexel University College of Medicine, Philadelphia, PA, United States of America
| | - B Sokhansanj
- McKool Smith Hennigan, P. C., Redwood Shores, CA, United States of America
| | - G L Rosen
- Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, United States of America.
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Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection. PLoS One 2016; 11:e0149521. [PMID: 26901316 PMCID: PMC4769325 DOI: 10.1371/journal.pone.0149521] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 02/02/2016] [Indexed: 12/17/2022] Open
Abstract
Objective To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. Perspective Public insurer for all hospital and physician services. Setting Ontario, Canada. Methods A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. Results Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. Conclusion Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective.
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Avila MB, Avila NP, Dupont AW. Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection. F1000Res 2016; 5. [PMID: 26918176 PMCID: PMC4755406 DOI: 10.12688/f1000research.7109.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/25/2016] [Indexed: 12/17/2022] Open
Abstract
Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies.
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Affiliation(s)
- Meera B Avila
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, 77030, USA
| | - Nathaniel P Avila
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, 77030, USA
| | - Andrew W Dupont
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, 77030, USA
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48
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Shin JY, Ko EJ, Lee SH, Shin JB, Kim SI, Kwon KS, Kim HG, Shin YW, Bang BW. Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation. Intest Res 2016; 14:83-8. [PMID: 26884739 PMCID: PMC4754527 DOI: 10.5217/ir.2016.14.1.83] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Revised: 03/10/2015] [Accepted: 03/16/2015] [Indexed: 01/01/2023] Open
Abstract
Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%–30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.
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Affiliation(s)
- Jun Young Shin
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Eun Jung Ko
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Seung Ho Lee
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Jong Bum Shin
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Shin Il Kim
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Kye Sook Kwon
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Hyung Gil Kim
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Yong Woon Shin
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Byoung Wook Bang
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
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Múñez E, Ramos A, Baños I, Cuervas-Mons V. [Fecal transplantation for the treatment of relapsing diarrhea associated with Clostridium difficile infection in a liver transplantation patient]. Med Clin (Barc) 2016; 146:e3-4. [PMID: 26343156 DOI: 10.1016/j.medcli.2015.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 06/02/2015] [Accepted: 06/04/2015] [Indexed: 11/16/2022]
Affiliation(s)
- Elena Múñez
- Unidad de Enfermedades infecciosas, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España; Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España.
| | - Antonio Ramos
- Unidad de Enfermedades infecciosas, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España; Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| | - Isolina Baños
- Unidad de Trasplante Hepático, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España; Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| | - Valentín Cuervas-Mons
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España; Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España; Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, España
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50
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Meehan AM, Tariq R, Khanna S. Challenges in management of recurrent and refractory Clostridium difficileinfection. World J Clin Infect Dis 2016; 6:28. [DOI: 10.5495/wjcid.v6.i3.28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 04/28/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
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