Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With RecurrentClostridium difficileInfection

Abstract

IMPORTANCE Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, −1.6% [95% CI,-10.5% to ϱ]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI,-5.2% to ϱ]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.

Cryopreservation of artificial gut microbiota produced with in vitro fermentation technology

“…To restore the microbial balance, transfer of faecal microbiota from a healthy donor (FMT) to diseased patients has been suggested as a therapeutic strategy. The success of FMT in treating RCDI has been demonstrated in several studies, with cure rates exceeding 90% (van Nood et al ., 2013; Kelly et al ., 2016; Lee et al ., 2016). Use of FMT as a therapy for other gastrointestinal disorders such as IBD has been proposed (Vermeire et al ., 2016).…”

New and emerging therapies for Clostridium difficile infection

“…59,60 Freeze-thawed versus fresh faeces delivered via an enema achieved rates of clinical resolution without recurrence up to 13 weeks compared with that were not significantly different in perprotocol (83.5% vs. 85.1%) and mITT (75.0% vs. 70.3%) populations. 59 However, about one third of the subjects in each treatment group, who were ultimately classified as resolved according to the study protocol, required two FMTs. It is a relatively common finding that repeat FMT administration is required to prevent recurrences.…”

Treatment of Clostridium difficile infection: a national survey of clinician recommendations and the use of faecal microbiota transplantation

“…These preparations, which are non-inferior to freshly prepared samples with regard to rates of clinical resolution, can be stored and available for use as needed. 10 This approach is a worthy consideration where a national stool banking service is not in operation.…”