scholarly journals A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3234
Author(s):  
Tanya M. Monaghan ◽  
Niharika A. Duggal ◽  
Elisa Rosati ◽  
Ruth Griffin ◽  
Jamie Hughes ◽  
...  

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

2021 ◽  
Vol 14 (01) ◽  
pp. 016-020
Author(s):  
Juliana Peloso Signorette ◽  
Rômulo Tadeu Dias de Oliveira ◽  
José Maria Montiel ◽  
Priscila Larcher Longo

Abstract Objective This study aimed to perform a comprehensive review of clinical trials using fecal microbiota transplantation in cases of Clostridioides difficile infection. Methods This manuscript reviews clinical studies published from 2003 to 2020 at the Scientific Electronic Library Online (SciELO Brazil), Latin American and Caribbean Health Sciences Literature (LILACS) and US National Library of Medicine (MedLine/PubMed) databases using the descriptors antibiotic/antimicrobial, Clostridium difficile/Clostridioides difficile, intestinal microbiota/intestinal microbiome and fecal transplantation. Results Interventions on microbiota include the use of probiotics, prebiotics, and fecal microbiota transplantation as therapeutic methods. Results show that fecal microbiota transplantation is an excellent alternative for the treatment of recurrent C. difficile infections.


2019 ◽  
Vol 8 (6) ◽  
pp. 580-584
Author(s):  
Jillian M Cotter ◽  
Maribeth R Nicholson ◽  
Larry K Kociolek

Abstract Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.


Author(s):  
Caroline Zellmer ◽  
Mohamad R A Sater ◽  
Miriam H Huntley ◽  
Majdi Osman ◽  
Scott W Olesen ◽  
...  

Abstract Fecal microbiota transplantation (FMT) is recommended therapy for multiply recurrent Clostridioides difficile infection. We report adverse events in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin–producing Escherichia coli (STEC). No patients died of FMT-transmitted STEC. Improved screening can likely avoid future transmission.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Elvira Garza-González ◽  
Soraya Mendoza-Olazarán ◽  
Rayo Morfin-Otero ◽  
Andrea Ramírez-Fontes ◽  
Patricia Rodríguez-Zulueta ◽  
...  

Aim. In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI). Methods. We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing. Results. We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor’s pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041). Conclusion. Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.


2021 ◽  
Vol 10 (24) ◽  
pp. 5822
Author(s):  
Daniel Popa ◽  
Bogdan Neamtu ◽  
Manuela Mihalache ◽  
Adrian Boicean ◽  
Adela Banciu ◽  
...  

Background: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI. Methods: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI. Results: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode. Conclusions: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.


2019 ◽  
Vol 8 (7) ◽  
pp. 1036 ◽  
Author(s):  
Jae Hyun Shin ◽  
Ashley S. Chaplin ◽  
R. Ann Hays ◽  
Glynis L. Kolling ◽  
Sheila Vance ◽  
...  

Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infections (rCDIs). We assessed the benefits of a multidisciplinary C. difficile clinic for screening FMT eligibility in patients with rCDI. Patients seen at the University of Virginia Complicated C. difficile Clinic (CCDC) underwent comprehensive evaluation for possible FMT. Patients were eligible for FMT if there was history of greater than two episodes of rCDI. Patients were evaluated for the outcome after evaluation in the clinic. A total of 113 patients were evaluated: 77 were eligible for FMT, of which 25 patients did not undergo FMT. The rate of recurrence at three months and all-cause mortality were 4.5% and 7% for patients who received FMT and 16.7% and 12.5% for eligible patients who did not receive FMT. There were 36 patients who were not eligible for FMT, with two or fewer recurrences and a recurrence rate of 8.8% and all-cause mortality of 6%. One in three patients screened for FMT had a nutritional deficiency diagnosed, with zinc deficiency being most common (20%). Additional diagnoses, including inflammatory bowel disease, were made during the evaluation. FMT is a highly effective treatment for rCDI, most notably in patients with multiple recurrences. A systematic approach for evaluating patients with rCDI helps identify patients who benefit most from FMT and those who have other conditions.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 10 (3) ◽  
pp. 389
Author(s):  
Eleftheria Kampouri ◽  
Antony Croxatto ◽  
Guy Prod’hom ◽  
Benoit Guery

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.


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