Clostridioides difficile-Infection (CDI)

2022 ◽  
Author(s):  
Jennifer Moisi
Keyword(s):  
Developed Countries ◽  
The United States ◽  
Fecal Microbiota ◽  
Oral Route ◽  
Incidence Rates ◽  
Phase Iii ◽  
Fecal Microbiota Transplant ◽  
Variable Effect ◽  
Clostridioides Difficile ◽  
Hygiene Measures

Clostridioides difficile is a Gram positive, spore-forming bacillus colonizing the lower gastrointestinal tract. Use of antibiotics, older age, and underlying diseases contribute to changes in the microbial flora of the gut, which may lead to the production of toxins that cause C. difficile infection (CDI), with symptoms ranging from mild to moderate diarrhea to severe diarrhea, pseudomembranous colitis, toxic megacolon and sepsis. CDI is difficult to treat and has a high risk of recurrence. The fecal-oral route is the predominant mode of C. difficile transmission. The highest CDI incidence rates are reported from developed countries, particularly the United States, but limited disease awareness and surveillance capacity may lead to underestimation of disease burden elsewhere. Treatment consists of stopping ongoing antibiotic treatment, specific anti-CDI antibiotics and fecal microbiota transplant (FMT). CDI recurrence can be prevented by an anti-toxin B monoclonal antibody, bezlotoxumab. Various hygiene measures should be applied but they are costly and of variable effect. A candidate vaccine directed at the C. difficile toxin failed in the past, possibly due to a change in the epitope through inactivation or to a suboptimal immunization schedule. Currently, only one vaccine candidate based on genetically and chemically detoxified toxins A and B is in phase III studies.

scholarly journals 1211. Response to Fecal Microbiota Transplant (FMT) in Refractory Clostridioides difficile Infection (CDI) is Modest Compared to Recurrent CDI in Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren
Keyword(s):  
Health System ◽  
Complete Resolution ◽  
Fecal Microbiota ◽  
Inpatient Setting ◽  
University Of Virginia ◽  
Cure Rate ◽  
Fecal Microbiota Transplant ◽  
Safety And Efficacy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

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

scholarly journals Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

2021 ◽  
Author(s):  
Ning-Jiun Jan ◽  
Noah Oakland ◽  
Pankaj Kumar ◽  
Girija Ramakrishnan ◽  
Brian W. Behm ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Fecal Microbiota Transplantation ◽  
Alpha Diversity ◽  
The United States ◽  
Fecal Microbiota ◽  
Peripheral Blood Mononuclear ◽  
Clostridioides Difficile ◽  
Rdna Sequencing ◽  
Clostridioides Difficile Infection ◽  
The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients

2021 ◽  
Author(s):  
Nirja Mehta ◽  
Tiffany Wang ◽  
Rachel J. Friedman-Moraco ◽  
Cynthia Carpentieri ◽  
Aneesh K. Mehta ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Fecal Microbiota Transplantation ◽  
Organ Transplant ◽  
Fecal Microbiota ◽  
Solid Organ Transplant ◽  
Pathogen Transmission ◽  
Solid Organ ◽  
Fecal Microbiota Transplant ◽  
Donor Screening ◽  
Clostridioides Difficile

In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI), however guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.

scholarly journals 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

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S841-S842
Author(s):  
Annie S Hong ◽  
Wen Yuan Yu ◽  
Jenny M Hong ◽  
Mohamed Azab ◽  
Gordon V Ohning ◽  
...  
Keyword(s):  
Systematic Review ◽  
Proton Pump ◽  
Primary Outcome ◽  
Fecal Microbiota Transplantation ◽  
Case Reports ◽  
Fecal Microbiota ◽  
Cochrane Library ◽  
Fecal Microbiota Transplant ◽  
Clostridioides Difficile ◽  
Significant Difference

Abstract Background Current 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. Methods We 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. Results Out 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. Conclusion We 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.

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

2019 ◽  
Vol 26 (9) ◽  
pp. 1415-1420 ◽  
Author(s):  
Raseen Tariq ◽  
Molly B Disbrow ◽  
John K Dibaise ◽  
Robert Orenstein ◽  
Srishti Saha ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Microbiota Transplantation ◽  
Median Number ◽  
Fecal Microbiota ◽  
Indeterminate Colitis ◽  
Clinical Predictors ◽  
Fecal Microbiota Transplant ◽  
Clostridioides Difficile ◽  
Inflammatory Bowel

Abstract Background 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. Methods 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. 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. Conclusions 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.

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