Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent<i>Clostridium difficile</i>Infection: A Systematic Review and Meta-analysis

Tariq, Raseen; Pardi, Darrell S.; Bartlett, Mark; Khanna, Sahil

doi:10.1093/cid/ciy721

Cited by 139 publications

(89 citation statements)

References 29 publications

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“…Clinical intervention trials are finally the critical test for the practical value of microbiome research. The success of faecal transplantation in C. difficile infection is a sign of hope (Tariq et al, 2019), but we need to decipher how it works mechanistically, both to achieve an industrial product and to understand why faecal transplantation works less well in other gastroenterology diseases (Imdad et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…It would certainly be desirable that future microbiomedisease association studies conduct power calculations with realistically anticipated effect sizes in their published results, as routinely done in the protocols for clinical trials. Such approaches plus meta-analyses will help to distinguish true from spurious associations to allow focusing on promising microbiota-disease associations that lead the field from hype to hope (McKenney & Pamer 2015), with meta-analyses of faecal transfer in C. difficile infection serving as an example (Tariq et al, 2019). Gilbert et al (2016) distinguished three categories of microbiota-disease associations: predictable associations (e.g.…”

Section: Underpowered Studies and Meta-analysesmentioning

confidence: 99%

“…One notable exception is faecal transplantation for the treatment of recurrent Clostridium difficile infections (CDI). However, despite clear data on its efficacy (Tariq et al, 2019), its development into a commercial product meets regulatory hurdles (Vyas et al, 2015;Verbeke et al, 2017), and the FDA has recently issued a safety alert pertaining to its use (https://www.fda.gov/vaccines-blood-biologics/ safety-availability-biologics/important-safety-alert-regard ing-use-fecal-microbiota-transplantation-and-risk-seriousadverse). Furthermore, the basic concept of this approach predates microbiome research (de Vos, 2013), and defined bacterial strains for recurrent CDI (Tvede and Rask-Madsen, 1989;Tvede et al, 2015) still need to be developed into registered products.…”

Section: Introductionmentioning

confidence: 99%

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Problems with the concept of gut microbiota dysbiosis

Brüssow

2019

Microbial Biotechnology

173

137

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Summary The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning ‘dysbiosis’ that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case–control studies are underpowered necessitating more meta‐analyses that sort out consistent from spurious dysbiosis–disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe–microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

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Section: Discussionmentioning

confidence: 99%

Section: Underpowered Studies and Meta-analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Problems with the concept of gut microbiota dysbiosis

Brüssow

2019

Microbial Biotechnology

173

137

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“…Two recent meta analyses on randomized controlled trials found consistent conclusions that enema was less efficient than oral or colonoscopy administration of fecal microbiota transplantation, and had efficacy equivalent to capsules or colonoscopy. No difference was seen between fresh and frozen stool 134135. In a systematic review published by Tariq et al, the authors concluded that fecal microbiota transplantation was associated with a lower cure rate in randomized controlled trials compared with open label and observational studies,135 and attributed this to the heterogeneity of the recurrence definition, but also to the inclusion of microbiota based drugs (SER-109), or administration by enema.…”

Section: Treatmentmentioning

confidence: 99%

Clostridioides difficile: diagnosis and treatments

Guery

Galpérine

Barbut

2019

BMJ

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Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available.

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“…Several randomized controlled trials and meta-analyses have demonstrated the improved efficacy of oral vancomycin over oral metronidazole for CDI treatment, and the likely benefit of fidaxomicin over oral vancomycin at preventing recurrence [117][118][119][120]. In a 2013 meta-analysis, cure rates for CDI with FMT were found to be near 90% [121]; however, this primarily included observational studies, and a more recent meta-analysis of randomized trials suggested that cure rates may be closer to 67%, with variability in outcomes dependent on route of FMT administration [122]. Bezlotuxumab, a monoclonal antibody against C. difficile toxin B was approved by the FDA in October 2016 for treatment and prevention of recurrent CDI in adults [123]; however, this drug has not yet been recommended for routine use in the current guidelines.…”

Section: Updates In Treatment Of Clostridium Difficile Infectionmentioning

confidence: 99%

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

Santos

Rhee

Czapka

et al. 2020

JCM

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Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key "safety net" in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible "safety net" for these immunocompromised hosts.

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Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for RecurrentClostridium difficileInfection: A Systematic Review and Meta-analysis

Cited by 139 publications

References 29 publications

Problems with the concept of gut microbiota dysbiosis

Problems with the concept of gut microbiota dysbiosis

Clostridioides difficile: diagnosis and treatments

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

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