Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

Introduction The National Institute of Health and Care Excellence recommend the use of faecal microbiota transplantation (FMT) for recurrent or refractory Clostridium difficile infection (CDI), as studies have shown it to be a highly effective therapy with a primary cure rate of over 90%. 1 We aimed to conduct a National survey to explore current practice of FMT and the challenges faced by hospitals in setting up this novel treatment strategy. Methods UK gastroenterologists, microbiologists and infectious disease physicians were invited to take part in a National survey by completing an online questionnaire over a five month period from October 2015. Results A total of 255 responses were obtained, of which 219 were evaluable. These came from 124 microbiologists/infectious disease clinicians and 95 gastroenterologists. The survey covered 130 independent sites: 112 acute NHS Trusts in England, 9 hospitals in Scotland and 9 hospitals in Wales. Only 28% (36/130) had performed FMT for refractory or recurrent CDI, of which 58% (21/36) of sites had experience of performing FMT for over 1 year, but only 19% (7/36) had treated at least 10 patients. 67% (24/36) made FMT on site while 33% (12/36) obtained FMT from elsewhere to administer at their hospital. Apart from one site that used FMT for refractory ulcerative colitis there were no other indications for its use. Of the 94 independent sites that did not perform FMT for refractory or recurrent CDI, 45% (42/94) believed that they were unable to do it due to lack of facilities, 38% (36/94) did not know where to start, however only 5% (5/94) felt reluctant to do it because of its perceived unpleasantness. Of those sites not performing the procedure, 70% (66/94) suggested that they would be keen to have support in setting up an FMT service for CDI locally. Only 29% (27/94) of the sites that did not perform FMT had referred their patients elsewhere; primarily to Glasgow, Birmingham and Exeter. Conclusion In the largest National survey done to date exploring the practice of FMT in UK, we have shown that only a quarter of responding sites performed FMT for recurrent or refractory CDI. There are significant challenges faced by hospitals in setting up this service. However, most welcomed support due to unfamiliarity with the perceived logistical hurdles. A central quality controlled and regulated FMT preparation, delivery and support service for the UK may be an efficient model to ensure continued and safe access to this novel treatment strategy for patients in the NHS. Reference 1 https://www.nice.org.uk/guidance/ipg485 Disclosure of Interest None Declared

Introduction: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridium difficile infection (CDI). Although immunocompromised patients are at high risk of CDI, the use of FMT may be limited owing to safety concerns. Since most FMT clinical trials exclude these patients, data on efficacy and safety of FMT in these patients are limited. We report results from a systematicreview and meta-analysis to evaluate the efficacy and safety of FMT in immunocompromised patients. Methods: A systematic search of MEDLINE, Embase and Web of Science was performed up to April 2018, followed by manual search of identified studies. We included case series, case-control or cohort studies, and clinical trials of FMT for CDI in immunocompromised patients with prevention of recurrent CDI as the primary outcome. Our primary analysis focused on calculating weighted pooled cure rate after one or more FMT. Results: A total of 18 studies were included. Among these, 566 immunocompromised patients underwent FMT for recurrent CDI. The various reason for immunosuppression included inflammatory bowel diseases, solid organ transplant (SOT), cancer, human immunodeficiency virus infection, graft versus host disease and hematopoietic stem cell transplants. Of the 566 patients, 430 had clinical cure of CDI with a pooled resolution rate after one FMT of 77.4% (95% CI, 71.6%-83.2%, I2= 57%).The pooled resolution rate increased to 91.5% (95% CI, 87.6%-95.4%, I2=21%) with multiple FMTs. No serious adverse events attributed to FMT were reported in any of the studies. On separating the 9 studies with immunosuppressed IBD patients, resolution after 1 FMT was reported in 328/412 patients, the pooled resolution rate 80.7% (95% CI, 76.6%-84.8%). In three studies with 103 SOT patients, FMT cured 58, with pooled cure rate of 50.2% (95% CI, 29.7%-70.6%). Conclusion: FMT appears to be safe and effective therapy for preventing recurrent CDI in immunocompromised patients. However, efficacy is lower in these patients compared to reported rates in immunocompetent patients. Efficacy improves with multiple FMTs. Although data were not available, repeat non-CDI antibiotic exposure in this population could potentially explain these findings. Studies are needed to explore best treatment practices in these patients including predictors of failed FMT which may identify patients who would benefit from early pre-emptive repeat FMT to prevent recurrent CDI

Clostridium difficile infection (CDI) constitutes an important cause of antibiotic-associated diarrhea. Recurrence after first-line treatment with antibiotics is high and fecal microbiota transplantation (FMT) may be effective for refractory and recurrent CDI. This series aims to describe the efficacy of FMT in the treatment of refractory and recurrent CDI. A prospectively recorded single-centre case series of patients with persistent or recurrent CDI treated with FMT between June 2014 and March 2015 was analyzed. Primary and secondary outcomes were defined as resolution of diarrhea without recurrence of CDI within 2 months after one or more FMT, respectively. A descriptive analysis was performed. 8 FMT were performed in 6 patients, 3 with refractory CDI and 3 with recurrent CDI. The median age of recipients was 71 years and 66.7% were women. One FMT was delivered through colonoscopy and the remaining 87.5% through esophagogastroduodenoscopy. One upper FMT was excluded due to recurrence of CDI after antibiotic exposure for a respiratory infection. The overall cure rate of FMT was total with lower route and 83.3% with upper route. Primary cure rate was achieved in 83.3% of patients and secondary cure rate was achieved in all patients. Median time to resolution of diarrhea after FMT was 1 day and no complications were reported during follow-up. FMT appears to constitute a safe and effective approach in the management of refractory and recurrent CDI. Difference between primary and secondary cure rates may result of insufficient restoration of intestinal microbiota with a single FMT.

Clostridium difficile infection (CDI) is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. The management of CDI has become a major challenge, given growing rates of recurrences and failures with standard antibiotic therapy. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is a paucity of data with regard to repeat FMT for primary non-response to this treatment, this study examined the outcome of multiple FMTs for recurrent CDI. Case records were reviewed for 94 patients who underwent FMT via retention enema for recurrent or refractory CDI during the period 2008-2012. Demographic information, treatment data, and clinical resolution rates were examined for single FMT and cumulative resolution was assessed for multiple FMTs in the context of ongoing symptoms. The cumulative clinical resolution following four or more FMTs was 86%. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92%. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6-24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.

INTRODUCTION: Fecal microbiota transplantation (FMT) is established as an effective treatment for recurrent Clostridioides (formerly Clostridium) difficile infection (CDI). Incidence and mortality from CDI are significantly higher in the elderly population (CDI is 10 times more common and 92% of CDI-related deaths occur in the elderly). Risk of cardiopulmonary complications from sedation prior to colonoscopy is increased in the elderly. Efficacy and safety of FMT via colonoscopy in the elderly are unknown. METHODS: A retrospective study comparing patients ≥75 years, and patients < 75 years who had FMT at Sanford Medical Center, Sioux Falls, SD, between 2013–2018. All patients underwent FMT via colonoscopy. Antibiotics prior to FMT, donor screening, preparation and delivery of FMT, and post-procedural follow up were based on a standardized protocol in our institution. Data on baseline characteristics, co-morbidities, antibiotics-associated with CDI, safety, and success rate of treatment (defined by resolution of symptoms and absence of CDI recurrence at 8 and 52 weeks) were collected. RESULTS: Of 59 patients, 17 (28.8%) were ≥75 years with a mean age of 84.4 years, and 42 (71.2%) were <75 years and a mean age of 46.4 years. Baseline characteristics of both groups are described in Table 1. Number of CDI before FMT, history of severe CDI, nosocomial CDI were similar. No fulminant CDI was reported in our study. In ≥75 years vs. <75 years, serum albumin was lower (3.4 vs 4 g/dl, P < 0.002) and hypertension was more common (52.9 vs 23.8%, P = 0.03). 80% of our study population had a history of antibiotics exposure prior to CDI, but there was no statistically significant difference between groups. Of antibiotics-associated with CDI, penicillins were more likely to be reported in ≥75 vs. <75 years (38.1 vs 5.9%, P = 0.014). Cephalosporins, macrolides, fluoroquinolones, and clindamycin were similar in both groups. Prior to FMT, both groups were treated similarly with vancomycin with or without taper, oral or intravenous metronidazole, or fidaxomicin. No major complications related to anesthesia or FMT via colonoscopy or deaths attributed to FMT were reported in our study. The success rates at 8 and 52 weeks in both groups were similar (76.5 vs. 83.3%, and 76.5 vs. 71.4%, respectively). CONCLUSION: Despite the increased risk of CDI and colonoscopy in the elderly population, success rate and safety of FMT appears to be equivalent between elderly and non-elderly. Prospective studies with larger sample size are needed.

Faecal microbiota transplantation (FMT) is the standard-of-care for recurrent or refractory Clostridioides difficile infection (CDI) [1]. Numerous variables impact the effectiveness of FMT, including donor, recipient, processing and administration factors. With the expanding use of FMT, it is important to determine the optimal treatment regimen to improve outcomes for patients with CDI and beyond. Paaske et al. carried out an eloquent multi-centre quality-improvement process, aimed at increasing CDI cure rates for patients undergoing FMT [2]. They implemented a number of interventions to enhance the effectiveness of FMT, showing that dose and donor matter. In this real-world study, eight-week cure rates of CDI-associated diarrhoea (CDAD) were increased across seven centres from 50% (95% confidence interval [CI] 45%–56%) to 59% (55%–63%), after the exclusion of three low-performing donors. Two donors had previous cure rates of less than 35%, and the third was observed to have a sudden decrease in effectiveness. Whilst the concept of an FMT super-donor has gained traction in inflammatory bowel disease, its relevance in CDI remains unclear, owing to consistently high cure rates [3]. The current data highlight the need for improved FMT regimens, with real-world efficacy lower than that reported in clinical trials [2, 4]. However, donor factors are not clearly elucidated in this study; rather donor performance is measured on prior outcomes. Donor factors previously associated with reduced efficacy include antibiotics within 3–12 months of donation, and donations with a Bristol Stool Form Scale of ≤ 3 [5]. Donor sex, BMI, smoking status, H. pylori status, birth-mode and donation-weight have not been found to influence the effectiveness of FMT in CDI. Selection of a super-donor has been trialled in one small pilot study in CDI, in which a single donor was selected from nine healthy candidates based on balanced Bacteroidetes/Firmicutes ratio, high stool butyrate concentration, and high alpha-diversity and phylogenetic-diversity [6]. CDI cure at week 10 was achieved in 10/10 patients with recurrent CDI, demonstrating that donor selection is feasible and may offer increased efficacy. Paaske et al. further increased their CDAD cure rates from 59% (55%–63%) to 72% (65%–77%) by implementing an optimised dosing regimen of two-dose capsule FMT [2]. Repeated FMT has been shown to increase clinical effect at week eight compared to single-dose FMT (91% vs. 84%), although it remains unclear which patients would benefit most from repeated doses [4]. In a separate cohort, Paaske and colleagues implemented a three-dose capsule regimen in high-risk patients, including those with fulminant CDI, patients expected to receive antibiotics in the week following FMT, and those aged 65 years or older with severe or antibiotic-refractory CDI [2]. This change did not result in increased overall efficacy (70% [60%–78%] vs. 67% [57%–76%]). FMT is highly effective in the treatment of CDI, but real-world cure rates lag behind those of well-designed clinical trials. Ongoing development of optimal donor, recipient and administration protocols is needed. Repeated dosing increases the efficacy of FMT in CDI, and emerging evidence supports donor selection in this population. To advance the field, we must now define microbial factors associated with efficacy. Perhaps the future is a rationally designed microbial therapeutic, with a defined and reproducible mechanism of action. D. Bogatic: conceptualization, writing – original draft, writing – review and editing. S. P. Costello: conceptualization, writing – original draft, writing – review and editing. R. V. Bryant: conceptualization, writing – original draft, writing – review and editing. The authors have nothing to report. D. Bogatic has received research support from The Gutsy Group and BiomeBank. S.P. Costello is a shareholder of BiomeBank. R.V. Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health; and is a shareholder in BiomeBank. This article is linked to Paaske et al paper. To view this article, visit https://doi.org/10.1111/apt.70395. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Objective: Fecal microbiota transplantation (FMT) is an emerging treatment for Clostridioides difficile infection (CDI) through reconstruction of the gut microbiota, but its impact in people with spinal cord injury (PWSCI) is limited. The aim of this paper is to report the use of FMT in a PWSCI with CDI. Methods: The FMT was conducted on October 30, 2019. Results: A 72-year-old man with T8 complete paraplegia from compression of the spinal cord due to an epidural hematoma was referred. He has known severe pancreatic enzyme insufficiency, malabsorption, and a history of recurrent CDI. Despite intensive dietetic treatment (probiotics, enteral nutrition, and parenteral nutrition), and multiple courses of antibiotics (vancomycin and fidaxomicin at various doses and durations) for CDI, he continued to be CDI-positive. His CDI was successfully treated after 2 colonoscopically delivered FMTs. At the 24-month follow-up, he remains CDI-negative and reports improved independence. Although there has been considerable variability in the criteria for the FMT and its mode of delivery, FMT can be an option to treat recurrent CDI. Conclusion: This case report reports a PWSCI with recurrent CDI who has been successfully treated with FMT and remains in long-term remission. It supports the consideration of FMT in PWSCI with CDI when antibiotic treatment has been unsuccessful.

Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.

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...

Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.

Introduction: Post-infectious irritable bowel syndrome (IBS-PI) is an increasingly recognized subset of IBS where symptoms arise following an acute gastrointestinal infectious illness. After C. difficile infection (CDI), IBS-PI symptoms can mimic recurrent infection. While fecal microbiota transplant (FMT) has been shown to be effective in reducing recurrence of CDI, reports on FMT’s impact on IBS have been mixed. Little has been reported on FMT’s effects on IBS-PI after CDI. This study aims to describe the experience of IBS-PI patients at our center who have undergone FMT. Methods: All patients at NorthShore University Health System receiving FMT for recurrent CDI were prospectively enrolled in our FMT registry. Demographic and clinical information, including pre-existing gastrointestinal disease, were reviewed. Patients were prospectively followed and queried on their clinical symptoms in the office or by phone at baseline, 24 hours, 7 days, 4 weeks and 6 months after FMT. Results: Between May 2015 and November 2017, 169 unique patients underwent FMT for recurrent or severe CDI (Table 1). The mean age of subjects was 67, and 123 (73%) were female. In total, 79 (46.7%) carried a diagnosis of IBS. Of those with IBS, 47 (27.8%) had documented clinical suspicion of IBS-PI by their GI physician, while 32 (18.9%) had pre-existing IBS. 35/47 (74.4%) of IBS-PI patients had symptoms consistent with IBS-D, 3 (6.4%) IBS-C, 6 (12.7%) IBS-M, and 3 (6.4%) unknown. FMT was effective in preventing CDI relapse in 142/169 (84%) of all patients, and 40/47 (85.1%) patients with IBS-PI. The questionnaire response rate for eligible patients with IBS-PI was 39/47 (83%) at 4 weeks after FMT, and 34/47 (72.3%) at 6 months (Table 2). At 4 weeks, 25 (64.1%) reported semi-formed, mushy/soft or loose stools, and 8 (20.5%) reported abdominal pain. At 6 months, 22 (64.7%) reported diarrhea, while 13 (38.2%) reported abdominal pain. 17 (39.5%) were treated with probiotics, 9 (20.9%) on dicyclomine, 7 (16.2%) on loperamide, and 2 (4.65%) on laxatives. Conclusion: IBS-PI is common in patients presenting for FMT for recurrent CDI. Response to FMT is similar amongst IBS-PI and non-IBS patients. However, almost 2/3 of IBS-PI patients continue to experience diarrheal symptoms up to 6 months after FMT, suggesting the limited role of FMT in IBS-PI. These results are relevant when setting expectations regarding symptom relief with the procedure. Further studies regarding IBS-PI management after recurrent CDI are needed.166_A Figure 1 No Caption available.166_B Figure 2 No Caption available.

Clostridium difficile (C. difficile​​​​​​) infection (CDI) poses a tremendous clinical challenge, especially in patients with recurrent disease and antibiotic resistance. Fecal microbiota transplantation (FMT) has become a new therapeutic strategy for restoring gut microbiota and decreasing CDI recurrence. The study aims to assess the clinical effectiveness of FMT in adult subjects with recurrent or refractory CDI, determine its effect on gut microbiome diversity, and track safety outcomes and rates of recurrence post-treatment. FMT was compared against standard antibiotic treatments to establish its efficacy in decreasing infection persistence and improving patients' quality of life. This study examines the efficacy, safety, and modulation of microbiota by FMT in an ensemble of 250 patients diagnosed with CDI, with equal gender distribution and a mean age of 55.61. Among the study participants, 131 (52.4%) underwent FMT by various routes of administration, including 66 (25.2%) through colonoscopy, 73 (29.2%) via a nasogastric tube, 60 (24.0%) via enema, and 54 (21.6%) through oral capsule administration. The success rate for FMT was reported as 88 (35.2%), partial success at 74 (29.6%), and treatment failure at 88 (35.2%). CDI recurrence was reported in 130 (52.0%) of patients after FMT. The gut microbiome enhanced diversity, measured in terms of the Shannon Diversity Index, increased significantly from 3.96 before FMT to 5.88 after FMT, thus indicating a favorable impact on gut microbial composition. Furthermore, 132 (52.8%) converted from C. difficile polymerase chain reaction (PCR) toxin positive to negative, corroborating successful pathogen clearance. On secondary outcomes, the quality of life in patients improved in 90 (36%), antibiotic dependence was reduced in 88 (35.2%), and hospitalization was lessened in 72 (28.8%). Inflammatory markers, such as white blood cell (WBC) counts and C-reactive protein (CRP), went downward but did not reach statistical significance. Logistic regression analysis identified age, severity of CDI, and prior exposure to antibiotics as the main predictors for the efficacy of FMT (p < 0.05). It is concluded that FMT is a promising alternative treatment for recurrent CDI through modulation of gut microbiota and decreasing the severity of infection. Future work is, however, required to establish treatment protocols with optimized results for long-term effectiveness and minimized recurrence risks.

Fecal microbiota transplantation (FMT) for Clostridium difficile infection: focus on immunocompromised patients.

BackgroundFecal microbiota transplantation (FMT) is a microbiota-based therapy that shows therapeutic potential in recurrent or refractory Clostridium difficile infections and other intestinal or extra-intestinal disorders. Nonetheless, adverse events (AEs) remain a major challenge in the application of FMT.AimTo review the AEs of FMT and to address the concerns of safety during the procedure.MethodsPublications were retrieved in the databases of Medline, Embase and Cochrane Library. AEs were classified according to their causality with FMT or their severity.ResultsA total of 7562 original articles about FMT were identified in this study, 50 of them fulfilled the inclusion criteria. Totally 78 kinds of AEs were revealed enrolled in these 50 selected publications. The total incidence rate of AEs was 28.5%. Among the 42 publications, 5 kinds were definitely and 38 kinds were probably related to FMT. The commonest FMT-attributable AE was abdominal discomfort, which was reported in 19 publications. For upper gastrointestinal routes of FMT, 43.6% (89/204) patients were compromised by FMT-attributable AE, while the incidence dropped to 17.7% (76/430) for lower gastrointestinal routes. In contrast, the incidences of serious adverse events (SAEs) were 2.0% (4/196) and 6.1% (40/659) for upper and lower gastrointestinal routes, respectively. A total of 44 kinds of SAEs occurred in 9.2% patients, including death (3.5%, 38/1089), infection (2.5%, 27/1089), relapse of inflammatory bowel diseases (0.6%, 7/1089) and Clostridium difficile infection (0.9%, 10/1089).ConclusionConsequently, both AEs and SAEs are not rare and should be carefully monitored throughout FMT. However, high quality randomized controlled trials are still needed for the more definite incidence of AEs of FMT.

Fecal microbiota transplantation (FMT) restores a diverse bacterial profile to the gastrointestinal tract and may effectively treat patients with Clostridium difficile infection (CDI). The objective of this systematic review was to evaluate the effectiveness of FMT in the treatment of CDI. Ovid MEDLINE, EMBASE, Web of Science, and Cochrane database were used. The authors searched studies with 10 or more patients examining the resolution of symptoms after FMT in patients with CDI. Reviews, letters to the editors, and abstracts were excluded. Participants were patients with CDI. Intervention used was FMT. Quality assessment was performed using the Cochrane risk of bias assessment tool. Results were synthesized using a narrative approach. Retrospective and uncontrolled prospective cohort studies suggest that FMT is a highly effective therapy for recurrent/refractory CDI, with clinical success rates ranging from 83% to 100%, which is similar to rates published by two randomized controlled trials. Fecal microbiota transplantation may be effectively administered via antegrade (upper gastrointestinal) or retrograde (lower gastrointestinal) routes of delivery. Fecal microbiota transplantation rarely results in major adverse events. However, diarrhea, cramping, and bloating commonly occur and are typically self-limited. Most studies were uncontrolled retrospective studies. Fecal microbiota transplantation should be considered in patients with recurrent episodes of mild to moderate CDI who have failed conventional antimicrobial therapy. There is insufficient evidence to recommend FMT for the treatment of severe CDI. Systematic review, level III.