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

Colleen R Kelly MD; FACG; Chioma Ihunnah MD; MPH; Monika Fischer MD; MSCR; Alexander Khoruts MD; Christina Surawicz MD; MACG; Anita Afzali MD; MPH; Olga Aroniadis MD; Amy Barto MD; Thomas Borody MD; PhD; FACG; Andrea Giovanelli BS; Shelley Gordon MD; PhD; Michael Gluck MD; Elizabeth L Hohmann MD; Dina Kao MD; John Y Kao MD; Daniel P McQuillen MD; Mark Mellow MD; FACG; Kevin M Rank MD; Krishna Rao MD; Arnab Ray MD; Margot A Schwartz MD; MPH; Namita Singh MD; Neil Stollman MD; FACG; David L Suskind MD; Stephen M Vindigni MD; MPH; Ilan Youngster MD; Lawrence Brandt MD; MACG

Disclosures

Am J Gastroenterol. 2014;109(7):1065-1071. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Clostridium difficile infection (CDI) is responsible for 15–25% of nosocomial antibiotic-associated diarrhea[1] and has increased rapidly in the past decade[2] to an incidence of 10.4 cases per 1,000 patient admissions.[3] Recurrence is a common management problem and occurs in up to 20% of patients after initial CDI treatment.[4] Current guidelines recommend a tapering course of vancomycin after a second recurrence; however, up to 60% of patients do not respond to this treatment strategy or develop further recurrence after the vancomycin is stopped.[5]

Initially described for treatment of pseudomembranous enterocolitis in 1958,[6] fecal microbiota transplant (FMT) has proven to be efficacious and safe in numerous case series[7] and a recently published clinical trial.[8] The use of FMT among immunocompromised (IC) patients with CDI has been limited due to concerns about its safety in this population. Published guidelines recommend avoidance of fecal transplant in solid organ transplant (SOT) recipients because of the theoretic potential for infection[9] and caution even against the use of probiotics in IC hosts because of the rare complication of superinfection (including bloodstream infections), which has been reported from these "nonpathogenic" organisms.[10,11] A recent guidance issued by the FMT working group specified that considerations for increased risk of adverse events (AEs) should be given to patients on major immunosuppressive agents and patients with decompensated liver cirrhosis, advanced HIV/AIDS, recent bone marrow transplant, or other causes of severe immunodeficiency.[12] Furthermore, the Food and Drug Administration/Center for Biologics Evaluation and Research recommended that patients who were IC for any reason be excluded from the first randomized trial of FMT in this country.[13] Successful treatment of CDI in two SOT recipients was recently described;[14] however, to date, no study has systematically investigated the safety and efficacy of FMT in a larger cohort of IC patients. We and colleagues at other medical centers offering FMT have treated a number of IC patients with FMT. By this collective experience we aim to describe rates of CDI cure in this population as well as AEs experienced by IC patients after FMT.

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