Emmalee Phelps

Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

Background:New treatments are needed as Clostridium difficile infection (CDI) is becoming increasingly formidable. Fecal microbiota transplantation (FMT) has a 90% success rate in the treatment of recurrent CDI. However, evidence regarding its safety, efficacy, and effect on disease activity in patients with inflammatory bowel disease (IBD) is lacking. Methods:This cohort study used data from 8 national and international academic centers. Patients with established IBD who underwent FMT for recurrent CDI were followed for a minimum of 3 months. The primary outcome was CDI recurrence at 3 months after FMT. The secondary outcomes were (1) IBD activity and severity at 3 months based on the judgment of the treating physician, endoscopic findings, and clinical disease activity scores; and (2) safety. Results:Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohns disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients. Serious adverse events included colectomy (1.4%), hospitalization for CDI (2.9%), hospitalization for IBD flare (2.9%), small bowel obstruction (1.4%), CMV colitis (1.4%), and pancreatitis (1.4%). Discussion:The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

OBJECTIVES:Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10–20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.METHODS:Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.RESULTS:Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26–15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55–9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18–1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1–2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.CONCLUSIONS:Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients.

Classifying Fecal Microbiota Transplantation Failure: An Observational Study Examining Timing and Characteristics of Fecal Microbiota Transplantation Failures

&NA; Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI), with cure rates higher than 80%.1–3 FMT failure is defined as diarrhea and a positive stool laboratory test for C difficile at any point during the 8‐week follow‐up period after FMT.4

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.

Response to Bodiwala and Skole

did not turn out to be an independent predictor of FMT failure in our model ( 2 ). Similarly, others have not found diverticulosis to be associated with an increased risk of recurrent CDI ( 3 ). Th erefore, we do not believe that redundant colon is a factor contributing to FMT failure based on the hypothesis of spore retention. To answer the question of whether bowel prep is associated with FMT outcome, we have analyzed the impact of bowel prep quality on FMT early failure among patients from one of the three centers ( N =179). Among these, 54% had good or excellent prep, 25% had fair, and 21% had poor or unsatisfactory colon prep. Approximately 18% of patients with good or excellent prep had FMT failure, while 27% of patients with fair prep and 36% of patients with poor or unsatisfactory prep had FMT failure, yielding a statistically marginal association between overall bowel prep quality and early (1-month) FMT failure ( P =0.064) in the univariate analysis. When the three important risk factors of FMT failure, including the severe or severe-complicated CDI indication, the number of CDI-related hospitalizations, and inpatient FMT, were added to the model, this marginal association disappeared. Compared to patients with excellent or good prep, the odds for FMT failure was 0.99 (95% confi dence interval (CI): 0.36– 2.78; P =0.99) for fair prep and 1.05 (95% CI: 0.37–3; P =0.924) for poor or unsatisfactory prep. Th ese results implied that bowel prep did not have any additional contribution in predicting the FMT outcome. Th e lack of importance of bowel prep for FMT failure aft er adjusting the three important predictors was due to its high correlation with CDI severity and inpatient status. Specifi cally, 7% of patients with good or excellent prep, 22% of patients with fair prep, and 37% of patients with poor or unsatisfactory prep had severe or severe-complicated CDI. In addition, 15% of patients with good or excellent prep were inpatient, while 33% of those with fair prep and 51% of those with poor or unsatisfactory prep were inpatients. Th ese results suggested that patients with poorer-quality prep tended to have more severe disease and were more likely to have inpatient FMT. When restricting the analyses for the outpatient FMTs ( N =132), similar results were found, where fair prep nal infusion, and the effi cacy of the colonic lavage was not assessed. It seems that the authors did not assess anatomy or bowel prep quality as risk factors for FMT failure. We are confi rming the confl ict of interest statement we have submitted. No changes to the confl ict of interest statement we have submitted. We believe these factors are possibly relevant and worth further analysis.