Dataset Information

Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.

ABSTRACT: INTRODUCTION:Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB such as extended spectrum beta-lactamase producing enterobacteriales (ESBL-E) and carbapenemase producing enterobacteriales (CPE) are more difficult to treat and are associated with an increased morbidity and mortality. Presently, there is no effective decolonisation strategy for these ARB. Faecal microbiota transplant (FMT) has emerged as a potential strategy for decolonisation of ARB from the human gut, however there is significant uncertainty about the feasibility, effectiveness and safety of using this approach. METHODS AND ANALYSIS:Prospective, randomised, patient-blinded, placebo-controlled feasibility trial of FMT to eradicate gastrointestinal carriage of ARB. Eighty patients with a recent history of invasive infection secondary to ESBL-E or CPE and persistent gastrointestinal carriage will be randomised 1:1 to receive encapsulated FMT or placebo. The primary outcome measure is consent rate (as a proportion of patients who fulfil inclusion/exclusion criteria); this will be used to determine if a substantive trial is feasible. Participants will be followed up at 1?week, 1?month, 3 months and 6 months and monitored for adverse events as well as gastrointestinal carriage rates of ARB after intervention. ETHICS AND DISSEMINATION:Research ethics approval was obtained by London-City and East Research Ethics Committee (ref 20/LO/0117). Trial results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER:ISRCTN registration number 34?467?677 and EudraCT number 2019-001618-41.

SUBMITTER: Merrick B

PROVIDER: S-EPMC7252984 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.

Merrick Blair B Robinson Emily E Bunce Catey C Allen Liz L Bisnauthsing Karen K Izundu Chi Chi CC Bell Jordana J Amos Gregory G Shankar-Hari Manu M Goodman Anna A Shawcross Debbie L DL Goldenberg Simon D SD

BMJ open 20200525 5

<h4>Introduction</h4>Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB such as extended spectrum beta-lactamase producing enterobacteriales (ESBL-E) and carbapenemase producing enterobacteriales (CPE) are more difficult to treat and are ...[more]

PMID: 32457083

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Project description:INTRODUCTION:Crohn's disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population. METHODS AND ANALYSIS:Forty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6?weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome. ETHICS AND DISSEMINATION:Ethics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children's Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montréal). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada's Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future. TRIAL REGISTRATION NUMBER:NCT03378167; pre-results.

Project description:BACKGROUND:The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response. METHODS AND ANALYSIS:This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40?cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study. ETHICS AND DISSEMINATION:The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University's Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants. TRIAL REGISTRATION NUMBER:ISRCTN 58082603; Pre-results.

Project description:We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

Dataset Information

Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.

Publications

Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.

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