Clostridioides difficile (C. difficile) is a major nosocomial pathogen but is also increasingly recognised as an important diarrhoeal pathogen in the community, not always associated with antibiotics. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for C. difficile (ESGCD) is a group of clinicians, scientists, and others from many European countries and further afield, who share a common interest in C. difficile. The aims of the Study Group are centred around raising the profile of  C. difficile infection (CDI) in humans and animals, fostering collaboration amongst centres in different European countries and providing a forum for discussing and disseminating information. One of the principal aims of the Study Group is to raise awareness of C. difficile infections in Europe. ESGCD has a particular interest in the development and dissemination of European guidance on prevention, diagnosis, and treatment of CDI. This chapter will discuss the organisation of ESGCD within the ESCMID Study Group structure, the origins of the Study Group, the aims, and objectives of the group, and will highlight some of the past and present activities of ESGCD in relation to these.

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OBJECTIVE: Treatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service.
METHODS: A decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature.
RESULTS: The ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy.
CONCLUSIONS: Compared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service.

METHODS: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery.
METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development.
CONCLUSIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for the management of Clostridioides difficile infections. The differences, sometimes subtle, between these guideline recommendations have caused some debate among clinicians. This paper delves into select key recommendations from each respective CPG and analyzes the differences and evidence associated with each. One primary difference between the CPGs is the preference given to fidaxomicin over vancomycin for initial treatment in non-severe and severe disease endorsed by IDSA/SHEA and ESCMID guidelines, while the ACG-sponsored CPGs do not offer a preference. The emphasis on cost effective data was also a noticeable difference between the CPGs and thus interpretation of the available evidence. When using guidelines to help support local practice or institutional treatment pathways, clinicians should carefully balance CPG recommendations with local patient populations and feasibility of implementation, especially when multiple guidelines for the same disease state exist.

METHODS: Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization.
METHODS: A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
CONCLUSIONS: In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April-June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.

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METHODS: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.
METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
CONCLUSIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.

This study aimed at evaluating in outpatients an algorithm for the laboratory diagnosis of Clostridioides (Clostridium) difficile infection (CDI), i.e., enzyme immunoassays (EIAs) detecting bacterial glutamate dehydrogenase (GDH) and toxin A/B, followed by polymerase chain reaction (PCR) analyses of samples with discordant EIA results. In total, 9802 examinations of stool samples by GDH and toxin EIAs performed in 7263 outpatients and 488 inpatients were analyzed retrospectively. Samples with discordant EIA results had been tested by a commercially available PCR assay detecting genes of the C. difficile-specific triose phosphate isomerase (tpi) and toxin B (tcdB). Concordant EIA results (686 C. difficile-positive, 8121 negative) were observed for 8807 (89.8%; 95% CI, 89.2-90.4%) samples. Of 958 samples with discordant EIA results, 895 were analyzed using PCR and 580 of 854 GDH-positive/borderline, toxin-negative samples (67.9%; 95% CI, 64.7-71.0%) were positive for tpi and tcdB, while 274 samples (32.1%; 95% CI, 29.0-35.3%) were tcdB-negative. In contrast, 35 of 41 GDH-negative, toxin-positive/borderline samples (85.4%; 95% CI, 71.2-93.5%) were tcdB-negative. Still, 6 samples (14.6%; 95% CI, 6.5-28.8%) yielded positive PCR results for both genes. In conclusion, around 90% of the samples were analyzed appropriately by only applying EIAs. Approximately one third of the PCR-analyzed samples were tcdB-negative; thus, patients most likely did not require CDI treatment.

OBJECTIVE: Clostridioides difficile infection (CDI) is a widely recognized condition associated with comorbidity and decreased patient quality of life. Certain professional medical organizations develop clinical practice guidelines for major diseases. This is done in an effort to streamline the universal clinical practice and ensure that a more accurate diagnosis and better treatments are offered to respective patients for optimal outcomes. However, as new data evolve, constant update of these guidelines becomes essential. While these guidelines provide up-to-date recommendations, they are not published around the same time; thus, their recommendations may vary depending on evidence available prior to guidelines preparation and publication.
METHODS: Recommendations and corresponding justifications from three major CDI guidelines between 2013 and 2017 were pooled and compared, and notable differences were highlighted while providing an insight and a final recommendation from a clinical standpoint.
RESULTS: Most recommendations were consistent among all three guidelines. One notable difference was in the specification of candidates for CDI diagnosis, where it would be recommended to mainly test patients with three or more diarrheal episodes over 24 h, if they had no other clear reason for the diarrhea. Another conflicting point was regarding the treatment of non-severe CDI where vancomycin can be considered for older or sicker patients; however, metronidazole still remains a reasonable option based on recent data, some of which were not cited in the most recent guidelines of IDSA/SHEA.
CONCLUSIONS: Overall, it is prudent to follow these guidelines with critical appraisal to fulfill the goal of achieving optimum patient outcomes.