Fecal Microbiota Transplantation Failure Research Articles

First-line treatment of fecal microbiota transplantation for immune-mediated colitis.

2660 Background: The management of moderate to severe IMC includes immunosuppression with steroids and/or biologic agents. Long-term immunosuppression increases the risk for infections and steroid induced toxicities. Fecal microbiota transplantation (FMT) is increasingly used for the treatment of refractory IMC. Front-line FMT treatment has not been studied for IMC but could potentially alleviate IMC symptoms while reducing unnecessary extended exposure to steroids. In this study, we present a case series of 12 patients who received front-line FMT for the treatment of IMC as part of a clinical trial. Methods: This study reports preliminary data from a prospective clinical trial (NCT0403861) exploring the efficacy and safety of FMT as a first-line treatment for IMC. To be included, patients had to 1) have symptoms of immune-mediated diarrhea or colitis grade ≥ 2 (per Common Terminology Criteria for Adverse Events v5) within 45 days of FMT and 2) not have received any immunosuppressive treatment for IMC or any other indication around the time of FMT. Results: Twelve patients have been enrolled in the trial thus far. Patients received front-line FMT in a median of 31 days (IQR: 16-67 days) from IMC onset. 10 (83.3%) patients had symptom improvement in a median of 5 days (IQR: 1-7 days) after FMT. The only FMT-related adverse events reported were fatigue, transient fever, self-resolving abdominal cramping, and gassiness in six patients (50.0%) within the first week of FMT. One of the six patients additionally had recurrence of a previously existing frequent UTI due to bladder cancer within a week of FMT. Most patients (10, 83.3%) stopped immunotherapy due to IMC. Seven patients (63.6%) were able to resume cancer treatment after FMT, with four (33.3%) resuming checkpoint inhibitors. None of the patients that resumed ICI had recurrence of their colitis requiring immunosuppression. Nine patients (75%) had colitis remission by the end of the study period, with one additional patient showing signs of symptom improvement but passing away before his outcome could be assessed. Only two patients (16.7%) required immunosuppression for persistent colitis after FMT failure. Conclusions: This study is the first to evaluate the safety and efficacy of front-line FMT for the treatment of IMC. Our preliminary results are promising and show that FMT can be an effective first-line treatment for IMC that can quickly provide symptom relief in a majority of patients while avoiding the use of steroids. Our results also suggest that front-line FMT can be delivered in a timely manner and can allow for the safe resumption of immunotherapy in this population that typically responds well to immunotherapy. While more patients are needed before any solid conclusions may be drawn, there is mounting evidence to suggest that first-line FMT may be a safe and effective alternative to the current standard of care treatment for IMC. Clinical trial information: NCT04038619 .

Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.

Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI.Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018.We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.

S223 Factors Related to Fecal Microbiota Transplant Failure in the Treatment of Recurrent C. difficile - A Single Center Retrospective Cohort Study

Introduction: Fecal Microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridioides difficile infection (CDI) with reported success rates of 80-90%. There are limited data on factors contributing FMT failure, particularly in the outpatient setting. Our objective was to describe FMT failure rates within one year and to evaluate factors associated with FMT failure. Methods: We conducted a retrospective cohort study of consecutive patients who had outpatient FMT at Baystate Medical Center, Springfield, MA from 12/14 through 9/18. We collected patient data including demographics, CDI related factors, comorbid conditions, medications and FMT route. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. diff toxin or PCR. IRB approval was obtained. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Due to low power, we present possible associations with p-values < 0.2. Results: 92 patients were included with a mean age of 64y. CDI severity (per IDSA guidelines) was mild/moderate in 73% and severe or fulminant in 27%. 69% of patients had been previously hospitalized for CDI and the most common FMT indication was recurrent CDI in 76%. FMT failure occurred in 25 of 92 (27%) of which half occurred within 21 days. Factors associated with FMT failure were immunosuppression (RR=2.90); current or previous malignancy (RR=2.50); prior hospitalizations (RR=2.42); and receipt of non-CDI antibiotics within 6 months of FMT (RR=2.80). None of the following factors were associated with risk of FMT failure: age, indication, CDI severity, history of colectomy, diabetes, prior radiation, history of appendectomy, probiotics prior to FMT, H2 antagonists or PPIs, ICU admission, inflammatory bowel disease, or route of FMT delivery (oral, NGT, colonoscopy). (Table) Conclusion: We have identified four factors associated with FMT failure for outpatients with recurrent CDI: immunosuppression, current or previous malignancy, prior CDI hospitalizations and non-CDI antibiotics within 6 months prior to FMT. Knowledge of the above factors may help inform treatment options for patients with recurrent or refractory CDI. Table 1. - Univariable analysis of associations between factors associated with FMT failure within one year Overall FMT FailureNo FMT FailureYes p- value Relative Risk N=92 N=67 N=25 (95% CI) Age at transplant (yrs) 63.9 65.1 60.7 0.319 0.92 (0.77 to 1.10) Male n=20 (21.7%) Female n=72 (78.3%) FMT Indication Recurrent CDI 70 (76.1%) 54 (77.1%) 16 (22.9%) 0.062 n/a Severe CDI 3 (3.3%) 3 (100.0%) 0 (0.0%) Fulminant Colitis 2 (2.2%) 2 (100.0%) 0 (0.0%) Recurrent and Severe CDI 17 (18.5%) 8 (47.1%) 9 (52.9%) CDI Severity Mild/Moderate 67 (72.8%) 51 (76.1%) 16 (23.9%) 0.415 Referent Severe 15 (16.3%) 10 (66.7%) 5 (33.3%) 1.40 (0.61 to 3.21) Fulminant Colitis 10 (10.9%) 6 (60.0%) 4 (40.0%) 1.67 (0.70 to 4.00) Prior Hospitalization Due to C. Diff No 29 (31.5%) 25 (86.2%) 4 (13.8%) 0.076 Referent Yes 63 (68.5%) 42 (66.7%) 21 (33.3%) 2.42 (0.91 to 6.40) Immunosuppression No 57 (62.0%) 48 (84.2%) 9 (15.8%) 0.003 Referent Yes 35 (38.0%) 19 (54.3%) 16 (45.7%) 2.90 (1.44 to 5.83) Current or Previous Malignancy No 70 (76.1%) 56 (80.0%) 14 (20.0%) Referent Yes 22 (23.9%) 11 (50.0%) 11 (50.0%) 0.012 2.50 (1.33 to 4.68) Antibiotics (6 mos. prior to cdiff; not treating c.diff.) No 32 (34.8%) 28 (87.5%) 4 (12.5%) 0.027 Referent Yes 60 (65.2%) 39 (65.0%) 21 (35.0%) 2.80 (1.05 to 7.46)

Effectiveness and Safety of Colonic and Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort. Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure. A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified. Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.

Development of a rational framework for the therapeutic efficacy of fecal microbiota transplantation for calf diarrhea treatment

BackgroundEstablishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.ResultsSpecifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor–recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.ConclusionsOverall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves.1SZe_1Amjvg5rTHsSJMvRbVideo abstract

Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection : An Updated Meta-analysis.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent/refractory Clostridioides difficile infection (CDI) with a 10% to 20% risk of recurrence after a single FMT. In this meta-analysis, we aimed to evaluate the predictors of FMT failure. A comprehensive search of MEDLINE, Embase, Cochrane, and Web of Science databases through July 2021 was performed. All studies that evaluated risk factors associated with FMT failure in a multivariate model were included. We calculated pooled odds ratios with 95% confidence intervals for risk factors reported in ≥3 studies using a random-effects model. Twenty studies involving 4327 patients (63.6% females) with recurrent/refractory CDI who underwent FMT were included. FMT failed in 705 patients (16.3%) with 2 to 3 months of follow-up in most studies. A total of 12 different risk factors were reported in a multivariate model in ≥3 studies. Meta-analysis showed that advanced age, severe CDI, inflammatory bowel disease, peri-FMT use of non-CDI antibiotics, prior CDI-related hospitalizations, inpatient status, and poor quality of bowel preparation were significant predictors of FMT failure. Charlson Comorbidity Index, female gender, immunosuppressed status, patient-directed donor, and number of CDI recurrences were not associated with FMT failure. Adequate bowel preparation at the time of FMT and optimizing antibiotic stewardship practices in the peri-FMT period can improve the success of FMT. Patients with nonmodifiable risk factors should be counseled about the risk of FMT failure. Our results may help develop a risk stratification model to predict FMT failure in CDI patients.

Family Stool Donation Predicts Failure of Fecal Microbiota Transplant for Clostridioides difficile Infection

<h3>Background and Aims</h3> Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for <i>Clostridioides difficile</i> infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT. <h3>Methods</h3> We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or <i>C difficile</i>–negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT. <h3>Results</h3> Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00–7.01 <i>P</i> = .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19–2.11 <i>P</i> = .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%. <h3>Conclusion</h3> Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.

Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3months (range 2-7.7months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.

Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.

Introduction:Treatment-refractory, acute graft-versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD.Methods:Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.Results:We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit (p = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure (p = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8+ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response.Conclusion:This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.

S0650 Fecal Microbiota Transplantation Decolonizes C. difficile in Patients With Inflammatory Bowel Disease and Concomitant C. difficile Infection

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk for C. difficile infection (CDI) and associated morbidity and mortality. Persistent C. difficile colonization occurs even after standard-of-care CDI antibiotics, and may contribute to the increased risk of recurrent CDI. Additionally, C. difficile colonization has public health consequences as patients may spread C. difficile and may lead to contact isolation and high-cost cleaning procedures in a healthcare setting. Fecal microbiota transplantation (FMT) is a promising therapy for recurrent CDI, however its efficacy among IBD patients is limited and the rate of decolonization is unknown. Accordingly, we assessed the safety, efficacy and C. difficile decolonization rate in in IBD patients with recurrent CDI following FMT. METHODS: This open-label, prospective single-arm multicenter cohort study enrolled patients from 4 tertiary care centers. Patients with IBD and 2 or more episodes of CDI received a single colonoscopic FMT from a universal stool bank. CDI testing (GDH/Toxin EIA and PCR) was performed pre-FMT, and at 1, 8, and 12 weeks post-FMT. The primary outcome was FMT failure through week 8 (defined as diarrhea and Toxin EIA positive for C. difficile). The secondary outcome assessed was C. difficile decolonization post-FMT (defined as negative PCR testing) at week 12. RESULTS: 50 participants were enrolled with a mean age of 43.3 years (range 21–91) and primarily female (n = 28, 56%), 14 of which had Crohn's disease (CD) (mean HBI = 6.4) and 36 had ulcerative colitis (UC) (mean Partial Mayo Score = 4.5). One patient did not receive FMT after enrollment. There were no treatment-related serious adverse events. Among the treated patients, 8% (4/49) participants experienced a confirmed FMT failure and received a second FMT. Two additional patients received a repeat FMT based on investigator discretion. In terms of C. difficile decolonization, 88.9% (40/45 eligible participants) experienced decolonization at week 12 follow-up period. CONCLUSION: To our knowledge, this is the largest prospective trial to assess the safety, efficacy and C. difficile decolonization rate of FMT in patients with IBD-CDI. This data suggests FMT is a safe and promising therapy for preventing CDI recurrence and achieving C. difficile decolonization which may have public health and economic implications. Future randomized controlled trials are needed.

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Issue Highlights

Issue Highlights

Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis

Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P= .003), had pseudomembranes (22.2% vs 0; P= .018), and underwent FMT as inpatients (45.5% vs 19%; P= .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P= .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P= .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.

Risk Factors that Predict the Failure of Multiple Fecal Microbiota Transplantations for Clostridioides difficile Infection.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood. We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure. A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT. This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.

BackgroundCure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.MethodsElectronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).ResultsTwenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).ConclusionsThis case series is a description of our center’s initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Fecal Microbiota Transplantation After Oral Vancomycin for Recurrent Clostridium difficile Infection

Purpose Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections in developed countries. Since 2000, there has been a significant increase in the incidence and severity of CDI. Treating recurrent CDI (rCDI) is challenging because the risk of recurrence increases with each subsequent episode. Several studies have demonstrated the benefit of fecal microbiota transplantation (FMT) in patients with rCDI with a cure rate ranging between 80% and 100%. The aims of this study were to review the FMT procedure and to identify the success rate of using 2-week oral vancomycin treatment before the FMT. Methods We performed a retrospective chart review for patients with rCDI who underwent an FMT procedure between 2014 and 2017. This study included patients who were diagnosed with rCDI and received 2-week oral vancomycin treatment before the FMT at Piedmont Columbus Regional Hospital. Results During the study period, 31 patients underwent 34 FMT procedures for rCDI. Twenty-nine patients were included in the study. Two patients (6.9%) had confirmed recurrence within 8 weeks after FMT, and 27 patients (93.1%) were considered treatment successes. No adverse events were noted. Both patients with FMT failures were offered treatment with a repeat FMT. Thirty-nine percent had mild to moderate rCDI. Most patients (69%) received upper FMT and 58.6% had fresh stool transplanted. Conclusions Fecal microbiota transplantation preceded by a standard 2-week vancomycin regimen for the treatment of patients with rCDI seems to be safe and effective. Further research is needed to explore optimal pretreatment regimens before the FMT to prevent FMT failure.

2434. Proton Pump Inhibitor Use on Efficacy of Fecal Microbiota Transplant Administered by Trans-Oral Routes for Clostridioides Difficile Infection: A Systematic Review and Analysis

BackgroundCurrent guidelines include fecal microbiota transplantation (FMT) in the management of recurrent Clostridioides difficile infections (CDI). However, FMT protocols are often facility dependent, and one variable is whether proton pump inhibitors (PPI) are given during preparation. Theoretically, PPIs reduce acidity and protects the transplanted microbiome for the most potent dose. On the other hand, PPIs have also been shown to negatively alter the microbiome and increase the risk of CDI. We conducted a systematic review of the literature to study PPI use on the efficacy of FMT delivered by the trans-oral route.MethodsWe searched PubMed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16th, 2018 using variations of keywords “fecal microbiota transplant” and “Clostridium difficile infection” with 4210 results. Two independent authors reviewed and excluded studies with unrelated topics, abstracts, case reports, or a low level of evidence. Studies with data on trans-oral FMT, PPI use, and the success rate were included. Final review yielded 11 studies including randomized controlled, case–control, cohort, retrospective and prospective trials. The primary outcome was the rate of FMT failure, defined as recurrence of symptoms with positive CDI testing at follow-up.ResultsOut of 233 included patients, 131 received a PPI per FMT protocol resulting in 27 cases of treatment failure. There were 23 cases of recurrence out of 102 patients who did not receive pre-FMT PPI. The primary outcome occurred in 20.6% in the group with PPI use vs. 22.6% in the group without (RR 0.91; CI 0.56 - 1.50). Limitations include the lack of studies directly comparing outcomes with respect to PPI use, and inability to control possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.ConclusionWe did not find a significant difference in efficacy between FMT protocols with regard to PPI use. It is possible that the theoretical benefit from increased survival of transplanted microbiota is offset by negative effects associated with PPIs. We suggest that routine use of PPIs in FMT be reconsidered in the absence of clear benefit. Further investigation is needed to optimize protocols for safety and efficacy. Disclosures All authors: No reported disclosures.

134 Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: Efficacy and Predictors of Success

INTRODUCTION: Clostridioides (formerly Clostridium) difficile infection (CDI) is the most commonly identified cause of healthcare-acquired infections in the united states (US). Fecal microbiota transplantation (FMT) is recommended for patients with three or more episodes of CDI. We aim to examine factors associated with the success of FMT in our institution. METHODS: A retrospective study of 59 patients who underwent FMT for CDI at Sanford Medical Center, Sioux Falls SD, the US 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, CDI, safety and success rate of FMT (defined by resolution of symptoms and absence of CDI recurrence at 8 and 52 weeks) were collected. RESULTS: Baseline characteristics of our study population are shown in (Table 1). The mean age at FMT was 57 years (19–92 years). There were 96% Caucasians and 76% of females. 40% and 35% had three and four episodes of CDI prior to FMT, respectively. Antibiotics were implicated in CDI development in 80% of subjects, most commonly: penicillins (28.8%), cephalosporins (28.8%) and fluoroquinolones (23.7%). 20% had inflammatory bowel disease (IBD), 47% were on proton pump inhibitors (PPIs), and 22% were on immunosuppressants at the time of FMT. Regarding antibiotics used to treat CDI: 58/59 patients received at least one trial of oral vancomycin (84% had vancomycin with six weeks taper), 72% had oral metronidazole and 15% had fidaxomicin. In patients with available data, the success rate of FMT at 8 and 52 weeks was 82.7% (48/58) and 82.6% (43/52), respectively. Two patients (3.4%) had a repeat FMT for CDI recurrence. No major complications, mortalities related to FMT were reported in our study. Failure of FMT at 8 and 52 weeks was associated with female gender, IBD, and immunosuppressants. In our study, IBD was associated with hypertension, PPI, immunosuppressants, and FMT performed without antibiotic coverage for CDI. CONCLUSION: FMT is safe and effective for recurrent CDI. In our study, we demonstrated that IBD and immunosuppressants, closely related variables, were associated with FMT failure. Previous studies have shown that IBD is associated with poor outcomes in CDI, and in FMT for CDI. However, it is not clear why FMT failures occurred more frequently in females. Prospective studies with larger sample size are needed.