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Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

ABSTRACT: BACKGROUND:Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI). AIMS:To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema. METHODS:In a single center, adults with ? 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied. RESULTS:Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema. CONCLUSIONS:The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product. TRIAL REGISTRATION:ClinicalTrials.gov NCT02449174.

SUBMITTER: Jiang ZD

PROVIDER: S-EPMC6214502 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

Jiang Zhi-Dong ZD Jenq Robert R RR Ajami Nadim J NJ Petrosino Joseph F JF Alexander Ashley A AA Ke Shi S Iqbal Tehseen T DuPont Andrew W AW Muldrew Kenneth K Shi Yushu Y Peterson Christine C Do Kim-Anh KA DuPont Herbert L HL

PloS one 20181102 11

<h4>Background</h4>Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).<h4>Aims</h4>To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.<h4>Methods</h4>In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) ...[more]

PMID: 30388112

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Project description:Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Project description:Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCEClostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.

Project description:BackgroundFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.ResultsIn total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.ConclusionsRegression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.

Dataset Information

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

Publications

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

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