The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

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.

30-Day postoperative COVID-19 outcomes in 398 patients from regional hospitals utilising a designated COVID-19 minimal surgical site pathway.

INTRODUCTION: Postoperative pulmonary complications and mortality rates during the COVID-19 pandemic have been higher than expected, leading to mass cancellation of elective operating in the UK. To minimise this, the Guy's and St Thomas' Hospital NHS Foundation Trust elective surgery hub and the executive team at London Bridge Hospital (LBH) created an elective operating framework at LBH, a COVID-19 minimal site, in which patients self-isolated for two weeks and proceeded with surgery only following a negative preoperative SARS-CoV-2 polymerase chain reaction swab. The aim was to determine the rates of rates of postoperative COVID-19 infection. METHODS: The collaboration involved three large hospital trusts, covering the geographic area of south-east London. All patients were referred to LBH for elective surgery. Patients were followed up by telephone interview at four weeks postoperatively. RESULTS: Three hundred and ninety-eight patients from 13 surgical specialties were included in the analysis. The median age was 60 (IQR 29-71) years. Sixty-three per cent (252/398) were female. In total, 78.4% of patients had an American Society of Anesthesiologists grade of 1-2 and the average BMI was 27.2 (IQR 23.7-31.8) kg/m2. Some 83.6% (336/402) were 'major' operations. The rate of COVID-19-related death in our cohort was 0.25% (1/398). Overall, there was a 1.26% (5/398) 30-day postoperative all-cause mortality rate. Seven patients (1.76%) reported COVID-19 symptoms, but none attended the emergency department or were readmitted to hospital as a result. CONCLUSION: The risk of contracting COVID-19 in our elective operating framework was very low. We demonstrate that high-volume major surgery is safe, even at the peak of the pandemic, if patients are screened appropriately preoperatively.

Healthcare resource use in hospitalized patients with carbapenem-resistant Gram-negative infections.

OBJECTIVES: Antimicrobial resistance (AMR) is a threat to global public health. Infections with resistant organisms are more challenging to treat, often delay patient recovery and can increase morbidity and mortality. Healthcare costs associated with treating patients with AMR organisms are poorly described. In particular, data for specific organisms, such as those harbouring carbapenem resistance, are lacking. METHODS: This was a retrospective, matched (1:1), single-centre, cohort study at a Central London hospital, comparing costs and resource use of 442 adult inpatients infected with either carbapenem-sensitive (CSO) or carbapenem-resistant organisms (CRO) over a two-year period. Resource use and micro-costing data were obtained from the hospital Patient, Education and Research Costing System (PERCS), and included both direct and indirect costs. RESULTS: Overall, the median healthcare-related cost of treating a patient with a CRO was more than double (£49,537 vs £19,299) that of treating a patient with a CSO. There were statistically significant increases in expenditure across 21 of 44 measured parameters including critical care costs, which accounted for the greatest proportion of overall costs in both groups. Infections were predominantly of the respiratory tract (41%) and caused by Pseudomonas aeruginosa (76%). CONCLUSIONS: Infection with CROs increases healthcare expenditure significantly. Many of the costs, including patient support, portering and catering, have been underappreciated in previous work. We additionally note that patients infected with CROs have longer hospital stays, and increased theatre operating times compared with patients infected with CSOs.

Individual- and community-level risk factors for ESBL Enterobacteriaceae colonization identified by universal admission screening in London.

OBJECTIVES: We evaluated risk factors for gastrointestinal carriage of Enterobacteriaceae which produce extended-spectrum ß-lactamases (ESBL-E), including individual-level variables such as antibiotic use and foreign travel, and community-level variables such as housing and deprivation. METHODS: In an observational study in 2015, all patients admitted to a London hospital group were approached to be screened for ESBL-E carriage using rectal swabs for 4 months. Patients completed a risk factor questionnaire. Those with a residential postcode in the local catchment area were linked to a database containing community-level risk factor data. Risk factors for ESBL-E carriage were determined by binary logistic regression. RESULTS: Of 4006 patients, 360 (9.0%) carried ESBL-E. Escherichia coli was the most common organism (77.8%), and CTX-M-type ESBLs were the most common genes (57.9% CTX-M-15 and 20.7% CTX-M-9). In multivariable analysis, risk factors for phenotypic ESBL-E among the 1633 patients with a residential postcode within the local catchment area were: travel to Asia (OR 4.4, CI 2.5-7.6) or Africa (OR 2.4, CI 1.2-4.8) in the 12 months prior to admission, two or more courses of antibiotics in the 6 months prior to admission (OR 2.0, CI 1.3-3.0), and residence in a district with a higher-than-average prevalence of overcrowded households (OR 1.5, CI 1.05-2.2). . CONCLUSIONS: Both individual and community variables were associated with ESBL-E carriage at hospital admission. The novel observation that household overcrowding is associated with ESBL-E carriage requires confirmation, but raises the possibility that targeted interventions in the community could help prevent transmission of antibiotic-resistant Gram-negative bacteria.

Existing and investigational therapies for the treatment of Clostridium difficile infection: A focus on narrow spectrum, microbiota-sparing agents.

Despite intense international attention and efforts to reduce its incidence, Clostridium difficile infection (CDI) remains a significant concern for patients, clinicians, and healthcare organizations. It is costly for payers and disabling for patients. Furthermore, recurrent CDI is particularly difficult to manage, resulting in excess mortality, hospital length of stay, and other healthcare resource use. A greater understanding of the role of the gut microbiome has emphasized the importance of this diverse community in providing colonization resistance against CDI. The introduction of fidaxomicin, which has limited effect on the microflora has improved clinical outcomes in relation to disease recurrence. There are a number of other new agents in development, which appear to have a narrow spectrum of activity whilst exerting minimal effect on the microflora. Whilst the role of these emerging agents in the treatment of CDI is presently unclear, they appear to be promising candidates.

Efficacy and acceptability of rectal and perineal sampling for identifying gastrointestinal colonization with extended spectrum ß-lactamase Enterobacteriaceae.

OBJECTIVES: We evaluated 'pre-laboratory' factors associated with the detection of extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) colonization including anatomical site, and staff and patient factors. METHODS: All admissions to a large London hospital over 3 months were approached to provide rectal and perineal swabs, which were cultured for ESBL-E using chromogenic media. ESBL-E detection rates for patient- or staff-collected rectal or perineal swabs were compared using McNemar tests. Binary logistic regression was used to explore factors associated with patients declining to provide a rectal swab. The impact of simplifying the verbal study description to patients to improve the participation rate was evaluated. RESULTS: Carriage of ESBL-E was significantly higher in rectal swabs than perineal swabs (7.8% of 4006 versus 3.8% of 4006, p <0.001), whether collected by staff or patients; 31.9% of 869 patients did not provide a rectal swab before the change in study description compared with 7.6% of 3690 patients afterwards (p <0.001). In multivariable analysis, factors associated with patients declining to provide a rectal swab were younger age (OR 0.99, 95% CI 0.99-1.00), female gender (OR 1.26, 95% CI 1.04-1.52), transfers from other hospitals (OR 1.77, 95% CI 1.07-2.93) or an unknown admission route (OR 1.61, 95% CI 1.09-2.37), being admitted before the change in study description (OR 0.39, 95% CI 0.31-0.48), and the staff member who consented the patient (p <0.001); ethnicity was not a significant factor. CONCLUSIONS: Rectal swabs are recommended for the detection of ESBL-E colonization. Staff and patient factors influence whether patients participate in prevalence studies, which may skew their findings.

Molecular detection of common intestinal parasites: a performance evaluation of the BD Max™ Enteric Parasite Panel.

The purpose of this study was to evaluate the level of agreement of the BD Max™ Enteric Parasite Panel (EPP) with microscopy for the detection of Giardia duodenalis, Cryptosporidium spp. and Entamoeba histolytica in stool samples. A total of 372 stool samples (partly collected on the basis of positive microscopy and partly unselected, consecutive sample submitted for parasite investigation) were tested with EPP according to manufacturer's instructions and also using microscopy according to standard techniques. Discrepant samples were further tested using PCR by the National Parasitology reference laboratory. Levels of agreement and laboratory turnaround times were measured and compared. Overall, positive and negative percent agreement was high between the two methods. However, microscopy resulted in four false positives and one false negative for G. duodenalis and two false positives for Cryptosporidium. Additionally, microscopy could not differentiate between E. histolytica and Entamoeba dispar. Median laboratory turnaround time was 65 hours for microscopy; results from EPP could be available after four hours. Blastocycstis hominis was detected by microscopy in one sample and would have been missed if only EPP was performed. The EPP was a good alternative to microscopy, detecting a small number of additional positives that were missed by microscopy. The assay is significantly faster than microscopy and allows laboratory workflows to be streamlined. The risk of missing parasites that are not included in the EPP appears to be minimal in the studied population; however, there may be certain patient groups who would benefit from microscopic examination of stools.

Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations.

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries. AIM: We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI. METHODS: A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement. FINDINGS: Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores. CONCLUSION: Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings.

Reduction in Clostridium difficile environmental contamination by hospitalized patients treated with fidaxomicin.

Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) (P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile.

Performance evaluation of the Verigene® (Nanosphere) and FilmArray® (BioFire®) molecular assays for identification of causative organisms in bacterial bloodstream infections.

Molecular assays designed to provide bacterial identification and detection of resistance genes directly from positive blood cultures can significantly reduce the time to definitive results. This has the potential to improve patient management and antimicrobial stewardship. However, the extent of such an impact is yet to be fully assessed. We tested two such assays, the Verigene® System Bloodstream Infection Tests (Nanosphere, Inc., Northbrook, IL, USA) (both Gram-positive and Gram-negative cartridges) and the FilmArray® Blood Culture Identification Panel (BioFire® Diagnostics, Inc., Salt Lake City, UT, USA). We compared their accuracy and speed of organism and resistance gene identification to conventional culture-based methods for 173 positive blood cultures. We also retrospectively determined, for organisms deemed not to be contaminants, the potential impact on antimicrobial prescribing. Both the Verigene® and FilmArray® assays accurately identified organisms, on average, 27.95 and 29.17 h earlier than conventional methods, respectively. There were a significant number of false-positives for Pseudomonas aeruginosa with the FilmArray® assay, which may have been related to contamination of the bioMérieux BacT standard anaerobic blood culture bottles, which the manufacturer has acknowledged. Both panels provided results significantly faster than conventional methods. In our setting, the extent of the potential positive impact on antimicrobial prescribing was modest (9 out of 173 samples). However, this may be an underestimation, since probable contaminants were not included in this analysis. In conclusion, both panels gave accurate results with significantly improved turnaround times.

Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection.

Microbes tend to attach to available surfaces and readily form biofilms, which is problematic in healthcare settings. Biofilms are traditionally associated with wet or damp surfaces such as indwelling medical devices and tubing on medical equipment. However, microbes can survive for extended periods in a desiccated state on dry hospital surfaces, and biofilms have recently been discovered on dry hospital surfaces. Microbes attached to surfaces and in biofilms are less susceptible to biocides, antibiotics and physical stress. Thus, surface attachment and/or biofilm formation may explain how vegetative bacteria can survive on surfaces for weeks to months (or more), interfere with attempts to recover microbes through environmental sampling, and provide a mixed bacterial population for the horizontal transfer of resistance genes. The capacity of existing detergent formulations and disinfectants to disrupt biofilms may have an important and previously unrecognized role in determining their effectiveness in the field, which should be reflected in testing standards. There is a need for further research to elucidate the nature and physiology of microbes on dry hospital surfaces, specifically the prevalence and composition of biofilms. This will inform new approaches to hospital cleaning and disinfection, including novel surfaces that reduce microbial attachment and improve microbial detachment, and methods to augment the activity of biocides against surface-attached microbes such as bacteriophages and antimicrobial peptides. Future strategies to address environmental contamination on hospital surfaces should consider the presence of microbes attached to surfaces, including biofilms.

Excess length of stay and mortality due to Clostridium difficile infection: a multi-state modelling approach.

BACKGROUND: The burden of healthcare-associated infections, such as healthcare-acquired Clostridium difficile (HA-CDI), can be expressed in terms of additional length of stay (LOS) and mortality. However, previous estimates have varied widely. Although some have considered time of infection onset (time-dependent bias), none considered the impact of severity of HA-CDI; this was the primary aim of this study. METHODS: The daily risk of in-hospital death or discharge was modelled using a Cox proportional hazards model, fitted to data on patients discharged in 2012 from a large English teaching hospital. We treated HA-CDI status as a time-dependent variable and adjusted for confounders. In addition, a multi-state model was developed to provide a clinically intuitive metric of delayed discharge associated with non-severe and severe HA-CDI respectively. FINDINGS: Data comprised 157 (including 48 severe) HA-CDI cases among 42,618 patients. HA-CDI reduced the daily discharge rate by nearly one-quarter [hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.61-0.84] and increased the in-hospital death rate by 75% compared with non-HA-CDI patients (HR: 1.75; 95% CI: 1.16-2.62). Whereas overall HA-CDI resulted in a mean excess LOS of about seven days (95% CI: 3.5-10.9), severe cases had an average excess LOS which was twice (∼11.6 days; 95% CI: 3.6-19.6) that of the non-severe cases (about five days; 95% CI: 1.1-9.5). CONCLUSION: HA-CDI contributes to patients' expected LOS and risk of mortality. However, when quantifying the health and economic burden of hospital-onset of HA-CDI, the heterogeneity in the impact of HA-CDI should be accounted for.

A parallel diagnostic accuracy study of three molecular panels for the detection of bacterial gastroenteritis.

Culture-dependent detection of gastroenteric bacteria is labour-intensive and does not provide results in a clinically relevant time frame. Several commercially available multiplex molecular panels are now available which may be more sensitive and could potentially provide rapid results. We compared the diagnostic accuracy, turnaround time and ease of use of three such molecular panels: the RIDA®GENE Bacterial Stool and EHEC/EPEC Panels (R-Biopharm AG, Darmstadt, Germany), the FTD® Bacterial Gastroenteritis Panel (Fast Track Diagnostics, Junglinster, Luxembourg) and the BD MAX™ Enteric Bacterial Panel (Becton Dickinson GmbH, Heidelberg, Germany). The results from 116 retrospective selected and 318 prospective unselected stool samples were compared with conventional culture-based techniques using a gold standard for a positive test of either culture or agreement in two of the three molecular panels. For most targets, the molecular panels were more sensitive than culture, detecting an additional 13 cases that culture missed. The laboratory turnaround time was under 3 h for all molecular panels, compared with 66.5 h for culture. The BD MAX™ panel was the fastest, easiest to use and most flexible.

Performance of the GeneXpert CT/NG assay compared to that of the Aptima AC2 assay for detection of rectal Chlamydia trachomatis and Neisseria gonorrhoeae by use of residual Aptima Samples.

There are currently no commercially available molecular assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal swabs with regulatory approval. We compared the Cepheid GeneXpert CT/NG assay with the GenProbe Aptima Combo2 assay, using 409 rectal swabs. Using Aptima as the gold standard, the sensitivity, specificity, and positive and negative predictive values of GeneXpert for the detection of C. trachomatis and N. gonorrhoeae were 86%, 99.2%, 92.5%, and 98.4% and 91.1%, 100%, 100%, and 98.6%, respectively. Despite significant dilution of samples prior to GeneXpert testing, the assay performed well with excellent specificity.

Lack of enhanced effect of a chlorine dioxide-based cleaning regimen on environmental contamination with Clostridium difficile spores.

Spores of Clostridium difficile may play a significant role in transmission of disease within the healthcare environment and are resistant to a variety of detergents and cleaning fluids. A range of environmental cleaning agents has recently become available, many of which claim to be sporicidal. We investigated the effect of changing to a chlorine dioxide-based cleaning regimen on C. difficile environmental contamination and patient infection rates. The prevalence of environmental contamination was unaffected with a rate of 8% (9/120) before and 8% (17/212) following the change. Rates of patient infection were also unchanged during these periods.