Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

Abstract

ObjectiveThe aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.MethodsWe designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10–14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario “Dr. Jose Eleuterio Gonzalez”. Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria).From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.ResultsWe included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients.Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.ConclusionThe results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors’ sample.

Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrentClostridium difficileinfections: a systematic review and Bayesian network meta-analysis of randomised controlled trials

“…The inconsistency in the results of the four included studies may be attributed to their small sample sizes, lack of blinding and variability between them on the basis of the process of collecting donor faeces, preparation of FMT, lag time between faeces collection and infusion, method of administration and SAT regimen. Furthermore, as evident from the findings of a previous RCT, patients who received FMT monotherapy for an initial episode of CDI without receiving prior antibiotics, retained more bacteroidetes in their gut than patients treated with antibiotics 22. These findings confirm the effect of antibiotics in attenuating intrinsic microbiota 5.…”

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice

“…Antibiotics are efficacious in the treatment of CDI93–95 and considered first-line therapy for an initial episode of CDI 96 97. FMT has been used in first-episode CDI and has comparable efficacy with antibiotics 98–100. Further research is required to assess the clinical efficacy of FMT in this setting.…”

The use of faecal microbiota transplant as treatment for recurrent or refractoryClostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

“…However, 37.5% (n=6/16) of the patients treated with FMT within a week of CDI diagnosis required further antibiotics and a second FMT within 1 month of the first FMT because of relapse 61. In a small pilot randomised trial, patients were randomised to either vancomycin or multi-donor FMT (administered either via upper or lower GI routes) as initial therapy for CDI; CDI resolution occurred in 88.9% (n=8/9) of patients with vancomycin, compared with 57.1% of patients (n=4/7) with one FMT, and 71.4% of patients (n=5/7) after two FMTs 62. Given the small size of these studies and equivocal results, the working group concluded that the reviewed studies did not support FMT as initial therapy for CDI.…”