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Faecal microbiota transplantation (FMT) is the transfer of screened and minimally processed faecal material from a ‘healthy’ donor to ‘diseased’ recipient. It has an established role, and is recommended as a therapeutic strategy, in the management of recurrent Clostridioides difficile infection (CDI). Recognition that gut dysbiosis is associated with, and may contribute to, numerous disease states has led to interest in exploiting FMT to ‘correct’ this microbial imbalance. Conditions for which it is proposed to be beneficial include inflammatory bowel disease, irritable bowel syndrome, liver disease and hepatic encephalopathy, neuropsychiatric conditions such as depression and anxiety, systemic inflammatory states like sepsis, and even coronavirus disease 2019. To understand what role, if any, FMT may play in the management of these conditions, it is important to consider the potential risks and benefits of the therapy. Regardless, there are several barriers to its more widespread adoption, which include incompletely understood mechanism of action (especially outside of CDI), inability to standardise treatment, disagreement on its active ingredients and how it should be regulated, and lack of long-term outcome and safety data. Whilst the transfer of faecal material from one individual to another to treat ailments or improve health has a history dating back thousands of years, there are fewer than 10 randomised controlled trials supporting its use. Moving forward, it will be imperative to gather as much data from FMT donors and recipients over as long a timeframe as possible, and for trials to be conducted with rigorous methodology, including appropriate control groups, in order to best understand the utility of FMT for indications beyond CDI. This review discusses the history of FMT, its appreciable mechanisms of action with reference to CDI, indications for FMT with an emerging evidence base above and beyond CDI, and future perspectives on the field.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin. In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals. Patients were randomly assigned (1:1) using an interactive web response system to receive extended-pulsed fidaxomicin (200 mg oral tablets, twice daily on days 1–5, then once daily on alternate days on days 7–25) or vancomycin (125 mg oral capsules, four times daily on days 1–10), stratified by baseline C difficile infection severity, cancer presence, age (≥75 years vs <75 years), and number of previous C difficile infection occurrences. The primary endpoint was sustained clinical cure 30 days after end of treatment (day 55 for extended-pulsed fidaxomicin and day 40 for vancomycin), assessed in all randomised patients who met the inclusion criteria and received at least one dose of study medication (modified full analysis set). Adverse events were assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT02254967. Between Nov 6, 2014, and May 5, 2016, 364 patients were enrolled and randomly assigned to receive extended-pulsed fidaxomicin or vancomycin. 362 patients received at least one dose of study medication (181 in each group). 124 (70%) of 177 patients in the modified full analysis set receiving extended-pulsed fidaxomicin achieved sustained clinical cure 30 days after end of treatment, compared with 106 (59%) of 179 patients receiving vancomycin (difference 11% [95% CI 1·0–20·7], p=0·030; odds ratio 1·62 [95% CI 1·04–2·54]). Incidence of treatment-emergent adverse events did not differ between extended-pulsed fidaxomicin (121 [67%] of 181) and vancomycin (128 [71%] of 181) treatment arms. One death in the vancomycin arm was considered by the investigator to be related to study drug. Extended-pulsed fidaxomicin was superior to standard-dose vancomycin for sustained cure of C difficile infection, and, to our knowledge, extended-pulsed fidaxomicin recurrence rates in this study are the lowest observed in a randomised clinical trial of antibiotic treatment for C difficile infection. Astellas Pharma, Inc.

All-cause 30-day mortality associated with C difficile infection has been reported to be in the region of 9-38%.3,4 Furthermore, cases are associated with excess length of hospital stay of approximately 7 days (and 12 days in severe cases).3C difficile infection usually occurs following disruption of the intestinal microbiota resulting from exposure to antibiotics. The main advantage of ridinilazole and other new drugs such as fidaxomicin and bezlotoxumab appears to be related to the reduction or prevention of recurrence. [...]the development of bedside tools that can be used in real time to predict accurately the risk of recurrent C difficile infection could be helpful. Biomedical Imaging Unit, Southampton General Hospital/Science Photo Library I have received grants and personal fees from Astellas, personal fees from BD, Luminex, Abbott, Orion Diagnostics, Qiagen, MSD, and DNA electronics, and non-financial support from Eurobiotix CIC, outside the submitted work. 1 RJ Vickers, GS Tillotson, R Nathan, Clostridium difficile, infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study, Lancet Infect Dis, 2017, published online April 28 2 KE Dingle, X Didelot, TP Quan, Clostridium difficile, infection in England: an observational study, Lancet Infect Dis, Vol. 17, 2017, 411-421 3 BG Mitchell, A Gardner, Clostridium difficile, : a...

Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.

Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. Methods This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. Results The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. Conclusions RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.

ObjectivesThis nested qualitative study (NQS) aimed to identify facilitators and barriers to the delivery of a substantive randomised controlled trial investigating the eradication of gastrointestinal tract carriage of antibiotic-resistant organisms using encapsulated faecal microbiota transplant (FMT).DesignNQS within a participant-blinded, randomised, placebo-controlled, single-centre, feasibility trial (RCT)—Feasibility of ERadicating gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO) (ISRCTN reg. no. 34 467 677)—with data collected via focus groups and analysed using thematic analysis.SettingRCT participants were recruited from a large academic tertiary referral hospital in central London. Focus groups were held at the hospital or via videoconferencing for those unable to travel.ParticipantsThis study included 13 FERARO study participants across two focus groups. 11 participants were under RCT follow-up and unaware of their treatment allocation, two participants had completed 6-month follow-up and knew whether they had received FMT or matched placebo. Additional data were opportunistically collected on reasons for declining RCT participation.ResultsParticipants found FMT to be an acceptable and holistic management strategy and noted positive impacts from RCT participation including enhanced personal health awareness and valuable support from the research team. The time and travel commitment presented the most substantial barrier to RCT participation. Many participants were motivated by a desire to give something back to the UK National Health Service and/or research. Patients’ current health status also influenced the decision-making process, and, while infrequently cited, the COVID-19 pandemic added extra complexity likely impacting individuals’ willingness to participate.ConclusionsWhile FMT is generally acceptable to participants, logistical barriers such as the time and travel commitment associated with RCT participation need consideration. Effective communication, personal connections and participant education on antimicrobial resistance are likely to be crucial for enhancing recruitment and retention in future trials.Trial registration numberISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Background Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. Objective Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. Methods Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. Results A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. Conclusion The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.