Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

Sex dependent differences of temporomandibular condylar bone mineral density distribution.

OBJECTIVE: The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. METHODS: CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. RESULTS: The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. CONCLUSION: Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial.

BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort. METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8 weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment. RESULTS: In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p < 0.0001; Chi-square test). Post-hoc analysis indicated that 91% (88/97) of evaluable RBX2660 responders remained CDI occurrence-free to 24 months after treatment demonstrating durability. RBX2660 was well-tolerated with mostly mild to moderate adverse events. The composition and diversity of RBX2660 responders' fecal microbiome significantly changed from before to after treatment to become more similar to RBX2660, and these changes were durable to 24 months after treatment. CONCLUSIONS: In this Phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group. Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence. Clinical Trials Registration NCT02589847 (10/28/2015).

Chronic voluntary caffeine intake in male Wistar rats reveals individual differences in addiction-like behavior.

Caffeine is the most widely consumed psychoactive substance in the world. However, there is controversy about whether becoming addicted to caffeine is possible and a lack of well-established animal models to examine caffeine consumption. The present study sought to establish a model of caffeine consumption in Wistar rats, identify different rat populations based on caffeine preference, and determine whether extended voluntary caffeine consumption produces compulsive-like caffeine intake and withdrawal symptoms. Male Wistar rats were used throughout the experiment. The optimal concentration of caffeine to maximize caffeine consumption and caffeine preference was determined. Rats were then given continuous access to caffeine, followed by intermittent access. Rats were tested for signs of withdrawal-like behavior by measuring mechanical nociception and irritability-like behavior. Rats were further examined for compulsive-like caffeine consumption using quinine adulteration. Dose-response testing indicated an optimal caffeine concentration of 0.3 mg/mL. During intermittent access to caffeine, the rats did not escalate their caffeine intake and instead exhibited a decrease in intake over sessions. Three groups of rats were identified based on caffeine preference (high, medium, and low) across continuous and intermittent access. These three groups of rats matched low (1 cup), medium (2 cups), and high (4 cups) levels of daily coffee consumption in humans. Caffeine-consuming rats did not exhibit differences in mechanical nociception or irritability-like behavior compared with controls. In high caffeine-preferring rats but not in medium or low caffeine-preferring rats, compulsive-like caffeine consumption was observed. The present study established a rodent model of caffeine consumption that resulted in large individual differences in caffeine intake, similar to humans. Compulsive-like caffeine consumption in high caffeine-preferring rats and differences in caffeine preference between groups suggest that caffeine may result in compulsive-like intake in a subpopulation of subjects. Further testing is necessary to determine the factors that contribute to differences in caffeine preference and compulsive-like intake.

Precision medicine and gut dysbiosis.

Clostridioides difficile Infection (CDI) is a leading cause of healthcare-associated infections in Canada, affecting the gastrointestinal tract which can lead to fever, abdominal pain, and diarrhea. Effective treatment for patients with Recurrent CDI (rCDI) can be achieved by Fecal Microbiota Transplantation (FMT) by introducing the gut micro-organisms of a healthy person (donor) into the bowel of the affected individual. Research has shown that an increase in the specific bacterial phyla post-FMT may be partly responsible for this gut restoration and elimination of disease. Furthermore, in understanding the key bacteria associated with successful FMT, full treatment plans can be developed for the individual needs of the patient by matching an infected individual with a donor possessing ideal microbiota for the specific patient. This development of precision medicine and more systematic adoption of FMT can be the next step toward more rapid resolution of rCDI.

Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.

Clinical Trials in Rheumatology.

Clinical trials evaluate the benefits and harms of medical interventions with the ultimate goal of establishing an evidence-based regimen that contributes to clinical decision making. Physicians benefit greatly from clinical research because it provides a greater understanding of epidemiology and health outcomes, and patients are given opportunities to participate in such trials. In this review, we discuss the challenges of conducting clinical trials investigating rheumatic diseases, including that of recruitment, finding the right trial, designing a budget, and performing a study in a timely manner. If done right, clinical investigation can be particularly rewarding both intellectually and financially.

Building an Adult Congenital Heart Program: Critical Components and Important Allies.

PURPOSE OF THE REVIEW: The purpose of this review is to illustrate specific challenges and opportunities in the building of an adult congenital heart disease (ACHD) program and to highlight critical components and important allies. RECENT FINDINGS: With more than 1.4 million adults with congenital heart disease in the USA alone, access to specialized, compassionate, high-quality comprehensive care requires a shift toward more aggressive expansion of ACHD care, especially in the context of sparse ACHD provider representation in the vast majority of adult medical centers. The effective build of an ACHD program requires measured escalation in management of ACHD complexity matched with cultivation of key resources and clinical services ranging from congenital cardiac surgery and interventional cardiology to acquired heart disease as well as partnerships with non-cardiac specialists. By reframing ACHD care as a shared goal between patients, providers, hospitals, pharmaceutical and device industry, and payers, a potent business model can be built around the developing ACHD program to facilitate acquisition of these key resources.

Management of Primary and Recurrent Clostridium difficile Infection: An Update.

BACKGROUND: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections (HAI) in the United States and Canada, and incidence rates have increased worldwide in recent decades. Currently, antibiotics are the mainstay treatments for both primary and recurrent CDI, but their efficacy is limited, prompting further therapies to be developed. Aim: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations.

Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.

PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD. RECENT FINDINGS: Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.

Results From a Randomized, Placebo-Controlled Clinical Trial of a RBX2660-A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection.

Background: Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. Methods: This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. Results: The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P = .152). One RBX2660 dose (group C) was superior to placebo (group B; P = .048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. Conclusions: One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. Clinical Trials Registration: NCT02299570.

Detection of DNA Amplicons of Polymerase Chain Reaction Using Litmus Test.

We report on a new colorimetric DNA detection method that takes advantage of the power of polymerase chain reaction (PCR) and the simplicity of the classic litmus test. The strategy makes use of a modified set of primers for PCR to facilitate ensuing manipulations of resultant DNA amplicons: their tagging with urease and immobilization onto magnetic beads. The amplicon/urease-laden beads are then used to hydrolyze urea, resulting in the increase of pH that can be conveniently reported by a pH-sensitive dye. We have successfully applied this strategy for the detection of two hypervirulent strains of the bacterium Clostridium difficile that are responsible for the recent increase in the global incidence and severity of C. difficile infections. Furthermore, the viability of this test for diagnostic applications is demonstrated using clinically validated stool samples from C. difficile infected patients.

Neurophysiological and Clinical Effects of Laparoscopic Retroperitoneal Triple Neurectomy in Patients with Refractory Postherniorrhaphy Neuropathic Inguinodynia.

BACKGROUND: Chronic postherniorrhaphy inguinal pain (CPIP) is a complex, major health problem. In the absence of recurrence or meshoma, laparoscopic retroperitoneal triple neurectomy (LRTN) has emerged as an effective surgical treatment of CPIP. METHODS: This prospective pilot study evaluated the neurophysiological and clinical effects of LRTN. Ten consecutive adult CPIP patients with unilateral predominantly neuropathic inguinodynia underwent three comprehensive quantitative sensory testing (QST) assessments (preoperative, immediate postoperative, and late postoperative). Pain severity, health-related function, and sleep quality were assessed over the course of a 6-month follow-up period. RESULTS: QST revealed marked increases in mechanical, pressure, thermal, and pain thresholds in the areas with maximum pain prior to LRTN surgery for the immediate (P < 0.01; mean 160.9 minutes, range 103 to 255 minutes after extubation) and late postoperative (P < 0.05; mean 27.9 days, range 14 to 78 days after surgery) assessments compared to baseline. Wind-up phenomena were eliminated postoperatively. LRTN provided robust group-level improvements of all clinical measures. No preoperative QST variables were found to be predictive of surgical outcomes. The positive change in heat pain threshold (preoperative compared to late postoperative) showed significant positive correlations with improvements of pain scores and function. CONCLUSIONS: LRTN may produce immediate, profound, and consistent positive effects across multiple mechanical, pressure, and thermal QST variables, and marked improvements of clinical outcomes in selected CPIP patients. These data contribute to the understanding of mechanisms involved in the success of LRTN. Large, high-powered studies are warranted to determine whether preoperative or repeated longitudinal QST may guide patient selection and predict effectiveness of LRTN.

Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection.

Background. Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods. A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results. VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions. Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

A Practical Method for Preparation of Fecal Microbiota Transplantation.

Clostridium difficile is a challenging infection that can be difficult to treat with antibiotic therapy. This chapter outlines the processing material for fecal microbiota transplantation (FMT), also known as stool transplant. Fecal transplantations are effective in treating recurrent C. difficile infection (CDI). FMT uses a stool sample collected from a healthy, screened donor to restore healthy microbiota in the colon of a patient with CDI for symptom resolution. Here, we describe a rapid method for FMT preparation that uses inexpensive and disposable materials.

Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling.

BACKGROUND: The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured. METHODS: Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples. RESULTS: We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95 % of the OTUs present at greater than 0.1 % abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list. CONCLUSIONS: We show that, through culture-enriched molecular profiling, the majority of the bacteria in the human gut microbiota can be cultured and this method revealed greater bacterial diversity compared to culture-independent sequencing. Additionally, this method could be applied for the targeted recovery of a specific bacterial group. This approach allows for the isolation of bacteria of interest from the gut microbiota, providing new opportunities to explore mechanisms of microbiota-host interactions and the diversity of the human microbiota.

Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial.

OBJECTIVES: Clostridium difficile infection (CDI) is a major public health concern. Treatment with commonly prescribed antibiotics is associated with high rates of recurrence after initial cure. Here, we present the efficacy and safety of surotomycin, an orally administered, minimally absorbed, selective bactericidal cyclic lipopeptide, compared with vancomycin, in patients with CDI. METHODS: In this Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial, participants received surotomycin 125 mg twice daily, surotomycin 250 mg twice daily or vancomycin 125 mg four times daily for 10 days. The primary efficacy outcome was clinical response at end of treatment. The registration number of the study on clinicaltrials.gov is NCT01085591. RESULTS: Clinical cure rates were similar among treatment groups (92.4% for surotomycin 125 mg twice daily, 86.6% for surotomycin 250 mg twice daily and 89.4% for vancomycin). Recurrence rates were 27.9% for surotomycin 125 mg twice daily, 17.2% for surotomycin 250 mg twice daily and 35.6% for vancomycin. The lower recurrence rate with surotomycin 250 mg twice daily versus vancomycin was statistically significant (P = 0.035). Recurrence rates were statistically similar between the surotomycin dose groups (P = 0.193). Rates of sustained clinical response at end of study were 66.7% for surotomycin 125 mg twice daily, 70.1% for surotomycin 250 mg twice daily and 56.1% for vancomycin. Incidence of adverse events was similar among treatment arms. CONCLUSIONS: Recurrence rates of CDI were lower with surotomycin with higher sustained clinical response rates compared with vancomycin, both of which may offer potential clinical benefits.

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.