Olga C. Aroniadis

Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent clostridium difficile infection

OBJECTIVES:Clostridium difficile infection (CDI) has increased to epidemic proportions over the past 15 years, and recurrence rates of 30–65% with failure to respond to multiple courses of antimicrobials are common. The aim of this study was to report the efficacy of fecal microbiota transplantation (FMT) in patients with recurrent CDI in five geographically disparate medical centers across the United States.METHODS:A multicenter long-term follow-up study was performed on the use of FMT for recurrent CDI. We were able to contact 77 of 94 eligible patients who had colonoscopic FMT for recurrent CDI ≥ 3 months before. Respondents completed a 36-item questionnaire via mail and/or phone that solicited pre-FMT, post-FMT, and donor data. Study outcomes included primary cure rate (resolution of symptoms without recurrence within 90 days of FMT) and secondary cure rate (resolution of symptoms after one further course of vancomycin with or without repeat FMT).RESULTS:Seventy-three percent of patients were women and the average age was 65 years. The long-term follow-up period ranged from 3 to 68 months between FMT and data collection (mean: 17 months). The majority of patients were living independently at the time of FMT; however, 40% were ill enough to be hospitalized, homebound, or living in a skilled nursing facility. Spouses and partners accounted for 60% of donors and 27% were either first-degree relatives or otherwise related to the patient. The average symptom duration before FMT was 11 months and patients had failed an average of five conventional antimicrobial regimens; nonetheless, 74% of patients had resolution of their diarrhea in ≤ 3 days. Diarrhea resolved in 82% and improved in 17% of patients within an average of 5 days after FMT. The primary cure rate was 91%. Seven patients either failed to respond or experienced early CDI recurrence (≤ 90 days) after FMT. Four of these patients were successfully treated with vancomycin with or without probiotics; two patients were treated unsuccessfully with vancomycin, but subsequent FMT was successful; one patient was not treated and died in hospice care of unclear cause. The secondary cure rate was 98%. All late recurrences of CDI occurred in the setting of antimicrobial therapy for treatment of infections unrelated to C. difficile. In all, 53% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur. While no definite adverse effects of FMT were noted, two patients had improvement in a pre-existing medical condition and four patients developed diseases of potential interest after FMT.CONCLUSIONS:FMT is a rational, durable, safe, and acceptable treatment option for patients with recurrent CDI.

Fecal Microbiota Transplant for Treatment of Clostridium difficile Infection in Immunocompromised Patients

OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.

Fecal microbiota transplantation: Past, present and future

Purpose of reviewFecal microbiota transplantation (FMT) re-establishes a balanced intestinal flora with resultant cure of recurrent Clostridium difficile infection (RCDI). FMT has also been used to treat other gastrointestinal (GI) diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation and a variety of non-GI disorders. The purpose of this review is to discuss the intestinal microbiota and FMT treatment of GI and non-GI diseases. Recent findingsIt is known that an imbalanced intestinal microbiota predisposes to CDI, IBD and IBS. The complex role of intestinal microbiota to maintain health, however, is a newer concept that is being increasingly studied. The microbiome plays an important role in cellular immunity and energy metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity and even some neuropsychiatric disorders. SummaryFMT is a highly effective cure for RCDI, but increased knowledge of the intestinal microbiota in health maintenance, as well as controlled trials of FMT in a wide range of disorders are needed before FMT can be accepted and applied clinically.

An overview of fecal microbiota transplantation: techniques, indications, and outcomes

Fecal microbiota transplantation has emerged as a highly effective treatment for recurrent Clostridium difficile infection with very early experience to suggest that it also may play a role in treating other GI and non-GI diseases. Donor screening guidelines are now available along with recommendations regarding routes of administration, diluents, stool weights, and volumes of stool to be used. This review aims to provide an overview of fecal microbiota transplantation, to summarize the data on its efficacy, and to provide the reader with an understanding of how to perform this novel treatment. Fecal microbiota transplantation (FMT) refers to infusion of a fecal suspension from a healthy individual into the GI tract of another person to cure a specific disease. FMT is by no means a new therapeutic modality; however, it did not receive public attention until recently, after several studies were published that showed stool is a biologically active, complex mixture of living organisms with great therapeutic potential for Clostridium difficile infection (CDI) and perhaps other GI and non-GI disorders. The revelations about the human microbiome that are being published by the Human Microbiome Project consortium are bringing the strength of science to clinical observation, thereby enhancing our understanding of just

The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals.

Objectives:Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients. Methods:A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (<12 wk) and late (≥12 wk) recurrence rates, and adverse events (AEs), including post-FMT diagnoses. Results:Of 168 eligible patients, 146 patients met the inclusion criteria. Of these, 68.5% were women. The mean (range) age was 78.6 (65 to 97) years and the follow-up period was 12.3 (1 to 48) months. FMT was performed for RCDI in 89 (61%), SCDI in 45 (30.8%), and CCDI in 12 (8.2%) patients. The primary and secondary cure rates were 82.9% and 95.9%, respectively. Early and late recurrences occurred in 25 and 6 patients, respectively. AEs included CDI-negative diarrhea in 7 (4.8%) and constipation in 4 (2.7%) patients. Serious AEs, recorded in 6 patients, were hospital admissions for CDI-related diarrhea, one of which culminated in death. New diagnoses post-FMT included microscopic colitis (2), Sjogren syndrome (1), follicular lymphoma (1), contact dermatitis and idiopathic Bence-Jones proteinuria (1), and laryngeal carcinoma (1)—all, however, were associated with predisposing factors. Conclusions:FMT is a safe and effective treatment option for RCDI, SCDI, and CCDI in elderly patients.

Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection: A Multicenter Experience.

Goal:Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI). Background:FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated. Study Methods:A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms. Results:A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (⩽90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (≥90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred. Conclusions:FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.

Is fecal microbiota transplantation (FMT) an effective treatment for patients with functional gastrointestinal disorders (FGID)

Despite its high prevalence and significant effect on quality of life, the etiology of functional gastrointestinal disorders (FGID), and specifically irritable bowel syndrome (IBS), has yet to be fully elucidated. While alterations in immunity, motility, and the brain‐gut axis have been implicated in disease pathogenesis, the intestinal microbiota are increasingly being shown to play a role and numerous studies have demonstrated significant differences from normal in the intestinal flora of patients with FGID, and between types of FGID. Fecal microbiota transplantation (FMT) is a curative therapy for Clostridium difficile infection (CDI), a disease hallmarked by intestinal dysbiosis, and FMT is now being explored as a means to also restore intestinal homeostasis in FGID.

Is Fecal Microbiota Transplantation the Answer for Irritable Bowel Syndrome? A Single-Center Experience

Is Fecal Microbiota Transplantation the Answer for Irritable Bowel Syndrome? A Single-Center Experience

Postoperative Clostridium difficile-associated diarrhea.

BACKGROUND Abdominal surgery is thought to be a risk factor for Clostridium difficile-associated diarrhea (CDAD). The aims of this study were to discern pre-operative factors associated with postoperative CDAD, examine outcomes after postoperative CDAD, and compare outcomes of postoperative versus medical CDAD. METHODS Data from 3904 patients who had abdominal operations at Montefiore Medical Center were extracted from Montefiores clinical information system. Cases of 30-day postoperative CDAD were identified. Pre-operative factors associated with developing postoperative CDAD were identified using logistic regression. Medical patients and surgical patients with postoperative CDAD were compared for demographic and clinical characteristics, CDAD recurrence, and 90-day postinfection mortality. RESULTS The rate of 30-day postoperative CDAD was 1.2%. After adjustment for age and comorbidities, factors significantly associated with postoperative CDAD were: antibiotic use (OR: 1.94), proton pump inhibitor (PPI) use (OR: 2.32), prior hospitalization (OR: 2.27), and low serum albumin (OR: 2.05). In comparison with medical patients with CDAD, postoperative patients with CDAD were significantly more likely to have received antibiotics (98% vs 85%), less likely to have received a PPI (39% vs 58%), or to have had a prior hospitalization (43% vs 67%). Postoperative patients with CDAD had decreased risk of mortality when compared with medical patients with CDAD (HR 0.36). CONCLUSION CDAD is an infrequent complication after abdominal operations. Several avoidable pre-operative exposures (eg, antibiotic and PPI use) were identified that increase the risk of postoperative CDAD. Postoperative CDAD is associated with decreased risk of mortality when compared with CDAD on the medical service.

On the role of ischemia in the pathogenesis of IBD: A review

&NA; Inflammatory bowel disease (IBD) is a chronic intestinal disorder comprising 2 distinct but often overlapping diseases: Crohns disease and ulcerative colitis. Although much research to identify the etiology of IBD has focused on genetic constitution, infectious causes, and immune dysregulation, its exact cause and pathogenesis remain incompletely understood. Mesenteric blood flow, the intestinal microcirculation, and intestinal ischemia also have been proposed as etiologic, although they remain less‐explored themes despite evidence suggesting a contributory role in IBD pathogenesis. The anatomy, architecture, and function of the splanchnic microcirculation will be reviewed here with regard to the development of intestinal microvascular ischemia, a pathologic process that appears to precede the classic changes that characterize IBD. Inflamm Bowel Dis 2009