Stool Bank Research Articles

Improving regulation of microbiota transplants

Policy should balance safety, efficacy, access, and research

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive

To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

Risk Factors for Symptoms of Post-Infectious Irritable Bowel Syndrome Following Fecal Microbiota Transplantation

Introduction: Fecal microbiota transplantation (FMT) by colonoscopy and capsules is effective for recurrent Clostridium difficile infection (CDI), regardless of donor source. Many patients report altered bowel habits and abdominal symptoms post-FMT despite CDI resolution. However, it is uncertain if functional illness post-FMT is directly related to FMT or to pre-existing factors. Currently, pre-screening of patients for IBS pre-FMT is not routinely conducted. We aimed to assess the relationship between post-FMT symptoms and (1) FMT delivery modality (2) donor source (patient selected/universal stool bank) and (3) recipient clinical features. Methods: We conducted a prospective cohort study at an academic center of adults with recurrent CDI treated with FMT by (1) colonoscopy with patient selected donor stool (2) colonoscopy from a universal stool bank or (3) capsules from a universal stool bank. In addition to pre-FMT screening for infections and detailed history, patients were evaluated using Rome III criteria and pre-CDI Bristol Stool Scale. Post-FMT assessment occurred at 8-weeks. Clinical cure was defined as absence of diarrhea or a negative CDI test. Clinically cured patients were assessed for gastrointestinal symptoms using modified Rome III criteria and stool consistency was assessed by the Bristol stool scale. Fisher's exact test for binary and student's t-test for continuous variables were performed for statistical analyses. Multivariate logistic regression was performed to identify predictors for post-FMT, postinfectious IBS symptoms. Results: 107 subjects underwent FMT: 42 by colonoscopy with a patient selected donor, 35 by colonoscopy with stool bank donors and 30 by FMT capsules. Among this cohort, 72.2% were female and had a mean age of 61.1+/-18.1 years. Importantly, 22 patients (20%) had pre-existing IBS by Rome III criteria. Fifteen (13.8%) did not achieve CDI cure with a single FMT. Among the clinically cured, 26 (27.9%) had symptoms of post-infectious IBS at 8-week follow-up: 9 with constipation and 17 with loose stools. In addition, 13 patients reported bloating or increased gas. Neither donor stool type nor delivery modality was associated with post-FMT IBS (p=0.39 and p=0.51, respectively). On univariate analyses, risk factors associated with post-FMT IBS included both pre-existing IBS and inflammatory bowel disease (IBD) (p=0.001 and 0.02, respectively) (Table 1). These remained significant in the multivariable model adjusting for age, sex, and FMT donor type (OR 5.9, 95%CI 1.8-19.1, p=0.002 and OR 4.5, 95%CI 1.2-17.9, p=0.03, respectively).Table: Table. Predictors of Post-Infectious IBS post FMTConclusion: Post-infectious IBS is common after CDI and many will experience these symptoms after an FMT; however, the only significant predictive factors were pre-existing IBS and IBD. Thus, all FMT patients should be screened for IBS and IBD at baseline to optimize post FMT expectation.

Improved Success Rate of Fecal Microbiota Transplantation With Dual Method of Administration in 2 Patients With Antibiotic-Refractory Complicated Clostridium difficile Infection in ICU Setting

Fecal microbiota transplantation (FMT) is well recognized as a treatment modality with a 90% success in patients with recurrent Clostridium difficile infection (RCDI). More recently, colonic FMT has been applied to severe CDI patients by Fisher et al with a success rate of 42%. We present two cases of complicated CDI in the setting of septic shock treated with a session of combined enteral and colonic FMT resulting in dramatic clinical response. 71-year-old man with a history of Clostridium difficile infection (CDI) presented with a 9-day history of profuse watery diarrhea associated with altered mental status and hypotension was admitted to ICU. Lab data showed elevated WBC, lactate and BUN. Stool testing for Clostridium difficile toxin and antigen was positive. He was started on IV metronidazole and oral vancomycin as well as vasopressor and intravenous hydration. His diarrhea persisted, and he became febrile with rising WBC to 44,000. Due to abdominal distention and pain, surgery suggested colectomy. Gastroenterology was consulted for alternative therapy with FMT. Colonoscopy showed severe pan-pseudomembranous colitis (Figure 1.1 and 1.2). Fecal filtrate from the hospital's stool bank was administered. 40 mL of filtrate was delivered into the jejunum and 60 mL of fecal filtrate was infused into the ascending colon. Within 72-hours, the patient's WBC improved along with mental status and hypotension with resolution of diarrhea. 51-year-old-man with a history of compensated liver cirrhosis was transferred to our hospital for septic shock associated with CDI. He was refractory to metronidazole, oral and rectal vancomycin as well as fidaxomicin. The patient was not a surgical candidate for colectomy due to clinical instability. Colonoscopy showed severe colitis in the rectosigmoid junction (Figure 1.3). Fecal filtrate of 100 mL was infused into the jejunum and 200 mL into the ascending colon. Within 48-hours, patient had a decline in WBC and vasopressor requirement. Patient had remarkable improvement in diarrhea within 48-hours. FMT has been reported as an alternative to subtotal colectomy in complicated CDI patients with dramatic therapeutic response. However, the efficacy appears to be low in the ICU setting. Delivery of FMT by combined enteral and colonic routes may improve success rates as it did in our two cases. Additional studies are needed to examine the effect of FMT by dual method of administration in complicated CDI patients.Figure: Pseudomembranous colitis in the transverse colon.Figure: Pseudomembranous colitis in the descending colon.Figure: Ulcerative proctitis.

Tu1066 - Pediatric Access to Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection in the United States and the Impact of Stool Banks: A Geospatial Analysis

Tu1066 - Pediatric Access to Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection in the United States and the Impact of Stool Banks: A Geospatial Analysis

Prospective Laboratory Evaluation of Fecal Microbiota Transplantation Donors: Results From an International Public Stool Bank

Prospective Laboratory Evaluation of Fecal Microbiota Transplantation Donors: Results From an International Public Stool Bank

The Impact of Stool Banks on Access to Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection in the United States: A Geospatial Analysis: 2016 ACG Presidential Poster Award

Introduction: Recurrent Clostridium difficile infection (rCDI) is a growing and costly public health threat. Fecal microbiota transplantation (FMT) has emerged as an effective treatment, though logistical barriers prevented widespread adoption. The availibility of FMT material from universal stool banks has expanded access to FMT for both providers and patients. However, the extent of this impact has not been well documented. We present a geospatial analysis of FMT adoption using material obtained from the largest public stool bank in the US. Methods: Data on health facilities or providers that performed FMT using material from a stool bank was available as a master list aggregated by US ZIP Codes (OpenBiome). Using standard GIS methods, duplicate geo-coded ZIP codes were removed given redundancy in catchment zones for driving times, and geocoded drive-time polygons were generated using network analysis for each FMT provider (TIGER/Line 2014, ArcMap 10.4, ESRI Business Analyst 2015). US census data (Oak Ridge National Laboratory LandScan 2014) with a 1 km2 resolution was used to estimate the population contained within each drive-time polygon. Zonal statistics were used to estimate percentage of the US population within a 1-hour, 2-hour, and 4-hour drive time from an FMT provider using simulated traffic for a Wednesday at noon for all facilities. Results: We identified 655 facilities that provided FMT from a public stool bank with 585 unique ZIP codes. Among these FMT programs, 94 were academic medical centers, 432 community hospitals, 102 private practices/ambulatory surgical centers and 27 operated by either a federal, state, or local government agency. Most of these sites are located in the Southern (230) and Western (177) United States, with fewer located in the Midwest (117), Northeast (127) and Pacific (4) regions. Overall, 99.7% of the population live within a 4-hour drive, 96.7% of the population within a 2-hour drive and 83.2% of the population within a 1-hour drive of a FMT provider using material from a stool bank (Figure 1). Only 40% of facilities previously performed FMT prior to using fecal material from a stool bank.Figure 1Conclusion: In the US, the advent of stool banks has enabled nearly universal access to FMT for rCDI, notably at facilities that may not have otherwise been able to offer the therapy. Given the reduction of time and distance to FMT that this access affords patients, further research should explore how universal access to FMT has impacted the epidemiology of CDI.

Clinical Effectiveness and Safety of Fecal Microbiota Transplantation in Children for Clostridium Difficile infection: Results from 9 Pediatric Centers in the United States: 2016 ACG Presidential Poster Award

Introduction:Clostridium difficile infection (CDI) is a major public health threat and a rising concern among the pediatric population. Fecal microbiota transplantation (FMT) is a cost-effective therapy for recurrent CDI and universal stool banks have emerged to enable safe and seamless access. Although FMT has been reported among children in small case series, a direct donor (e.g. parent) approach has primarily been employed. Accordingly, there is a paucity of pediatric safety and effectiveness data from stool banks. Methods: Quality assurance data on CDI classification, FMT delivery modality and clinical effectiveness was consecutively collected from 9 pediatric healthcare facilities in the United States between January 16, 2014 and June 1, 2016. Patients were treated with 250mL fecal microbiota preparation (FMP) for lower GI delivery or 30mL FMP for upper GI delivery. The primary outcome was physician-reported clinical cure as per standard of care follow-up. Safety data was assessed through mandatory adverse event (AE) reporting and graded according to NIH criteria. Descriptive statistics and Chi-square analysis for binomial variables was conducted. Results: Among consecutively collected reports, complete safety and effectiveness data was returned for 69 patients, which were included in these analyses. Overall, the clinical cure rate from physician-reported data across all delivery modalities and CDI classifications was 85.5%. Across the pediatric cohort, 69.6% (n=48) of patients were treated by lower GI delivery by colonoscopy (n=46) or enema (n=2) with a cure rate of 80.9%. Additionally, 30.4% (n=21) of the cohort was treated by upper GI delivery by nasogastric (n=11), nasoduodenal (n=1), nasojejunal (n=2) and EGD (n=7) with a clinical cure rate of of 87.5%. There was no statistically significant difference in clinical cure between lower and upper GI delivery (p=0.47). Specifically, clinical cure for colonoscopy (85.4%) and nasogastric delivery (85.1%) was not significantly different (p=0.99). On a priori subgroup analysis, there was no significant difference in clinical cure rate by CDI disease classification and FMP preparation type (Table 1). No adverse events were reported to OpenBiome.Figure 1Conclusion: To our knowledge this is the largest pediatric FMT cohort reported to date. This real-world clinical data suggests that FMT in pediatric CDI has a similar safety and effectiveness profile to FMT in adult CDI. Further long-term follow-up is required to evaluate the long-term safety profile.

Nutritional Composition of Stool Donorsʼ Diets Relative to That of the U.S. Population: Results from 44 Donors from an International Stool Bank for Fecal Microbiota transplantation

Nutritional Composition of Stool Donorsʼ Diets Relative to That of the U.S. Population: Results from 44 Donors from an International Stool Bank for Fecal Microbiota transplantation

Su1737 Clinical Efficacy of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection From an International Public Stool Bank: Results From a 1,406 Patient Multi-Center Cohort

Su1737 Clinical Efficacy of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection From an International Public Stool Bank: Results From a 1,406 Patient Multi-Center Cohort

Sa1093 Assessing the Landscape of Fecal Microbiota Transplantation Programs for Recurrent Clostridium difficile Infection: A Survey of Existing Practices Among Healthcare Centers Using an International Public Stool Bank

Sa1093 Assessing the Landscape of Fecal Microbiota Transplantation Programs for Recurrent Clostridium difficile Infection: A Survey of Existing Practices Among Healthcare Centers Using an International Public Stool Bank

Prospective Assessment of Donor Eligibility for Fecal Microbiota Transplantation at a Public Stool Bank: Results From the Evaluation of 1387 Candidate Donors

Prospective Assessment of Donor Eligibility for Fecal Microbiota Transplantation at a Public Stool Bank: Results From the Evaluation of 1387 Candidate Donors

Optimal screening and donor management in a public stool bank

BackgroundFecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank.ResultsCompared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand.ConclusionsMore frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0140-3) contains supplementary material, which is available to authorized users.

Late‐breaking abstracts

Late‐breaking abstracts

Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection.

Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT.

Novel Safety Features in Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: Quality Assurance and Adverse Events Workflow

Introduction: Recurrent Clostridium difficile infection is a major public health threat, and fecal microbiota transplantation (FMT) is a promising treatment. Despite widespread adoption, there remains heterogeneity in protocols used to ensure ongoing mitigation of disease transmission from donor to recipient. Accordingly, we present a standardized FMT safety framework emphasizing novel laboratory and clinical safeguards developed at a stool bank. Methods: To derive our quality control framework, we integrated best practices after a comprehensive literature review to determine donor assessment and stool processing protocols. Safety protocols were vetted in an iterative, Delphi-like process with content experts. Quarterly safety summits enabled quality assurance input and safety protocol validation from a 12-member clinical advisory board representing thought leaders in gastroenterology, infectious disease, and microbiology. Results: Once a donor passes robust pre-screening, three novel laboratory and clinical safety protocols are deployed to continuously monitor health and safety. First, in the laboratory each donation is visually assessed for stool pathology (melena, hematochezia, mucus are excluded) and quality (Bristol Stool Score 3-5 are accepted). Material is processed individually and sequentially in a Class II biosafety cabinet to eliminate mislabeling and cross-contamination. Contact surfaces are sanitized with 70% ethanol, sporicidal wipes and ultraviolet light. All prepared treatments are placed in a 60-day quarantine until donors pass a second set of clinical and laboratory screens to ensure health throughout the collection period and embed a seroconversion delay. An aliquot of every FMT treatment is preserved for two years to enable re-examination as required. Second, continuous donor health monitoring includes periodic, random clinical donor health assessments and laboratory testing. Donors are regularly educated about illness protocols and provided with 24/7 access to an on-call physician. Last, in the case of a possible adverse event, an a priori SAFE adverse events protocol has been developed (Figure 1). Aggregate safety data are disseminated quarterly to clinical partners and relevant regulators.Figure 1Conclusion: This FDA-reviewed safety protocol has been used to supply over 4,000 FMT treatments without any reported serious adverse events attributable to the FMT material. This framework holds promise as a potential standard for FMT.

The Cost-Effectiveness of Competing Strategies for Managing Multiply Recurrent Clostridium difficile Infection: Examining the Impact of Universal Stool Banks and Encapsulated Fecal Microbiota Transplantation

The Cost-Effectiveness of Competing Strategies for Managing Multiply Recurrent Clostridium difficile Infection: Examining the Impact of Universal Stool Banks and Encapsulated Fecal Microbiota Transplantation

Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data.

Faecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI) is greatly facilitated by frozen stool banks. However, the effect of frozen storage of stool for greater than 2months on the viability of stool bacteria is unknown and the efficacy of FMT is not clear. To evaluate the viability of bacteria in stool frozen for up to 6months, and the clinical efficacy of FMT with stool frozen for 2-10months, for the treatment of rCDI. Viability of six representative groups of faecal bacteria after 2 and 6months of storage at -80°C, in normal saline (NS) or 10% glycerol were assessed by culture on plate media. The clinical outcomes of 16 consecutive patients with rCDI treated with aliquots of stool frozen in 10% glycerol and stored for 2-10months were also examined. Viability at both 2 and 6months was similar to baseline, in specimens stored in 10% glycerol and at 2months in stool stored in NS, but was reduced by >1 log at 6months for Aerobes (P<0.01), total Coliforms (P<0.01) and Lactobacilli (P<0.01) in NS. Using stool frozen for 2-10months in 10% glycerol, the cure rate for rCDI was 88% with one FMT and 100% after repeat FMT in those who relapsed. Stool for faecal microbial transplant to treat rCDI can be safely stored frozen in 10% glycerol for at least 6months without loss of clinical efficacy or viability in the six bacterial groups tested.

Donor Recruitment for Fecal Microbiota Transplantation

Increasing demand for fecal microbiota transplantation (FMT) has created a need for stool banks sourced from long-term healthy donors. Here, we describe our experience in recruiting and screening fecal donors. Mailbox, newspaper, and online advertisements were used. Potential donors were required to satisfy a prescreen telephone conversation, pass blood and stool investigations, then undertake a screening interview including medical history, physical examination, and evaluation of donor selection criteria. One hundred sixteen potential donors were prescreened of whom 74 failed-47 declined based on study donation requirements (primarily related to frequency and duration of donations), 13 had medical comorbidities, 6 variant Creutzfeldt-Jakob disease risk factors, 8 for other reasons. Thirty-eight completed stool and blood testing-1 failed blood testing (indeterminate hepatitis C serology), whereas 15 failed stool investigations (5 Dientamoeba fragilis, 5 Blastocystis hominis, 1 B. hominis and D. fragilis, 1 Giardia intestinalis plus D. fragilis, 1 Norovirus plus Clostridium difficile toxin positive, and 2 leucocytes or erythrocytes on stool microscopy). Of the 18 potential donors proceeding to screening interview, 6 were excluded (3 body mass index >30, 1 illicit drug use, 1 uncontrolled anxiety and concerns regarding compliance, 1 irregular bowel movements after new medication commencement). In total, only 12 of 116 (10%) potential donors were enrolled as study donors. Recruitment of fecal donors for FMT is challenging with only a small percentage ultimately serving as donors. Many were unable or unwilling to meet the donor commitment requirements. A surprisingly large proportion of healthy asymptomatic donors failed stool testing, primarily due to gastrointestinal parasites.

OC-045 Faecal microbiota transplantation: implementing a new treatment for recurrent/refractory clostridium difficile infection using banked stool in a tertiary uk centre

Introduction Faecal microbiota transplantation is an effective treatment for recurrent/refractory Clostridium difficile infection (CDI). A randomised controlled trial reported sustained response in greater than 90% of patients, with an excellent safety profile. NICE approved the treatment as of March 2014. We introduced this new service in January 2015, setting up a stool bank to treat patients with recurrent CDI. We describe the process of initiating this service. Method Stool donors are recruited from non-clinical members of hospital staff or patient selected donors. Donors must be healthy with a BMI >50 g of fresh donated stool is diluted with 250 mls 0.9% normal saline and 12.5% glycerol, filtered to remove large particles and immediately frozen at –80 0 C. Frozen stool can be stored for up to 6 months, offers the benefit of being available on demand, and is as effective as freshly used stool. Recipients are informed of the risks of colonoscopy and the risk of acquiring an unrecognised transmissible disease. Standard bowel preparation is given and the transplant is delivered through the endoscope channel with 75% of the donor stool placed in the caecum, and the remainder in the right colon. Alternatively, infusion can be performed via a nasoduodenal tube. Results This pathway has been successfully implemented. Procedures are performed at the end of a list to allow subsequent deep cleaning of the endoscopy room, and donor stool is available in an ice box 30 min prior to procedure. Individuals are discharged home the day after the procedure, and contacted a week later to ascertain improvement in symptoms, and at 3-months for a second assessment including laboratory testing for C. difficile . Preliminary experience is promising with 100% of patients achieving clinical remission within a week of a single procedure. Conclusion Introduction of a faecal transplant service for CDI is feasible. As with all new treatments safety is paramount. Thorough screening of donors, traceability of transplants and long term follow up is essential. Disclosure of interest None Declared.