Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study

Singh, Rajendra; Groot, Pieter F. de; Geerlings, Suzanne E.; Hodiamont, Caspar J.; Belzer, Clara; Berge, Ineke J. M. ten; Vos, Willem M. de; Bemelman, Fréderike J.; Nieuwdorp, Max

doi:10.1186/s13104-018-3293-x

Cited by 84 publications

(59 citation statements)

References 18 publications

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“…One week after FMT, 3/8 with carbapenem-resistant Enterobacteriaceae and 3/9 with vancomycin-resistant Enterobacteriaceae had negative rectal swabs. A Dutch uncontrolled cohort study examining FMT for decolonization of ESBL-E carriage in 15 patients showed similar results with 3/15 (20%) patients being negative 4 weeks after FMT [15]. A further uncontrolled study from Poland reported successful eradication of intestinal carriage in 15 out of 20 (75%) patients with haematological disease colonized by CPE, ESBL-E or other MDRO 1 month after FMT [19].…”

Section: Discussionmentioning

confidence: 82%

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial

Huttner

Lastours

Wassenberg

et al. 2019

Clinical Microbiology and Infection

124

117

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Faecal microbiota transplantation Neomycin a b s t r a c t Objectives: Intestinal carriage with extended spectrum b-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. Methods: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 Â 10 6 IU 4Â/day; neomycin sulphate 500 mg 4Â/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35e48 days after randomization (V4). ClinicalTrials.gov NCT02472600. The trial was funded by the European Commission (FP7). Results: Thirty-nine patients (G ¼ 14; P ¼ 16; U ¼ 7; T ¼ 2) colonized by ESBL-E (n ¼ 36) and/or CPE (n ¼ 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4 e6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).

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Section: Discussionmentioning

confidence: 82%

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial

Huttner

Lastours

Wassenberg

et al. 2019

Clinical Microbiology and Infection

124

117

View full text Add to dashboard Cite

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“…Another small retrospective case-matched study of 20 patients in France showed 80% (8/10) of patients cleared CRE or CRE/Acinetobacter colonization 14 days after FMT versus 20% (2/10) in the control group [24]. In other small studies (n = 8 to 20) with various endpoints, the effectiveness of decolonization ranged from 20% to 93% [1,[25][26][27][28][29]. One study by Davido et al suggests that based on an 87% decolonization rate of VRE at three months, FMT should be further explored to combat outbreaks within hospitals [30].…”

Section: Fecal Microbiota Transplantationmentioning

confidence: 97%

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Feehan

Garcia‐Diaz

2020

Microorganisms

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Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.

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“…Moreover, the dissemination of ARGs and pathogenic AROs in patients hampers effective medical care of infections and results in longer hospitalization and higher medical expenditures [23]. Still, multiple studies report e cient reduction of ARGs and decolonization of AROs through microbiota transplantation [24,25].…”

Section: Introductionmentioning

confidence: 99%

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

Kwak

Choi

Hink

et al. 2020

Preprint

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Background. Intestinal microbiota restoration can be achieved by complementing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.Results. All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel ‘transplantation index’ metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.Conclusions. Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.Trial registration: NCT02299570. Registered 19 November 2014, https://clinicaltrials.gov/ct2/show/NCT02299570

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Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study

Cited by 84 publications

References 18 publications

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

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