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Item Fecal Microbiota Transplantation(Thieme, 2023-01-25) Cheng, Yao-Wen; Fischer, Monika; Medicine, School of MedicineFecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.Item Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis(Oxford University Press, 2021-07-23) Song, Yi Nong; Yang, David Yi; Veldhuyzen van Zanten, Sander; Wong, Karen; McArthur, Eric; Zhao Song, Claire; Ianiro, Gianluca; Cammarota, Giovanni; Kelly, Colleen; Fischer, Monika; Russell, Lindsey; Kao, Dina; Medicine, School of MedicineBackground: Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim: This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods: A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results: Two hundred and forty patients from 10 studies (8 case series, 1 case-control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion: FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.Item Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection(Thieme, 2020-03) Cheng, Yao-Wen; Fischer, Monika; Medicine, School of MedicineFecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as “ Clostridioides difficile ”) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.Item Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection(Oxford University Press, 2021-08-19) Allegretti, Jessica R.; Kelly, Colleen R.; Grinspan, Ari; Mullish, Benjamin H.; Hurtado, Jonathan; Carrellas, Madeline; Marcus, Jenna; Marchesi, Julian R.; McDonald, Julie A.K.; Gerardin, Ylaine; Silverstein, Michael; Pechlivanis, Alexandros; Barker, Grace F.; Blanco, Jesus Miguens; Alexander, James L.; Gallagher, Kate I.; Pettee, Will; Phelps, Emmalee; Nemes, Sara; Sagi, Sashidhar V.; Bohm, Matthew; Kassam, Zain; Fischer, Monika; Medicine, School of MedicineBackground: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited. Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling. Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04). Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.Item Microbiologic Approaches to Treating Inflammatory Bowel Disease(Millennium Medical Publishing, 2021-08) Fischer, Monika; Medicine, School of MedicineItem SARS-CoV-2 vaccines and donor recruitment for FMT(Elsevier, 2021) Ianiro, Gianluca; Mullish, Benjamin H.; Hvas, Christian Lodberg; Segal, Jonathan P.; Kuijper, Ed J.; Costello, Samuel P.; Kelly, Colleen R.; Allegretti, Jessica R.; Fischer, Monika; Iqbal, Tariq H.; Satokari, Reetta; Kao, Dina; van Prehn, Joffrey; Ng, Siew C.; Bibbò, Stefano; Dahl Baunwall, Simon Mark; Quraishi, Mohammed N.; Sokol, Harry; Zhang, Faming; Keller, Josbert; Masucci, Luca; Quaranta, Gianluca; Kassam, Zain; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni; Medicine, School of Medicine