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The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes. [ABSTRACT FROM AUTHOR]

The article discusses a study of the extent of Clostridium difficile infection in Europe. The study set up a network of 106 laboratories in 34 European countries, and tested stool samples of patients with suspected C. difficile infection or diarrhea that developed after hospital admissions. It was observed that the incidence of the infection varied across hospitals.

Objectives: The prevalence of Clostridioides difficile infection (CDI) has been shown to vary markedly between European countries, both in hospitals and in the community. Determining the true prevalence has proven challenging. Without systematic testing in hospitals, the unchecked transmission of CDI can lead to large outbreaks in more susceptible cohorts. We investigate the success of CDI surveillance and control measures across Europe, by examining the dynamics of disease spread from the community into a hospital setting. We focus on national differences, such as variability in testing and sampling, disease prevalence in communities and hospitals, and antimicrobial usage., Methods: We developed a stochastic, compartmental, dynamic mathematical model parameterized using sampling and testing rate data from COMBACTE-CDI, a multicountry study in which all diarrhoeal stool samples (N = 3163) from European laboratories were tested for CDI, and data for antimicrobial usage and incidence of hospital cases sourced from the European Centre for Disease Prevention and Control., Results: The framework estimates the prevalence of CDI among hospital patients across European countries and explores how national differences impact the dynamics, transmission, and relative incidence of CDI within the hospital setting. The model illustrates the mechanisms influencing these national differences, namely, antimicrobial usage rates, national sampling and testing rates, and community prevalence of CDI., Discussion: Differential costs for testing and practicalities of scaling up testing mean every country needs to consider balancing CDI testing costs against the costs of treatment and care of patients with CDI., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objectives: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections worldwide, resulting in a significantly increasing burden on the healthcare systems. However, Pan-European data about cost and resource utilization of CDI treatment do not exist., Methods: A retrospective analysis within the Combatting Bacterial Resistance in Europe CDI project was conducted based on resource costs for inpatient treatment and productivity costs. Country-specific cost values were converted to EURO referred to 1 January, 2019 values. Differences in price levels for healthcare services among the participating countries were adjusted by using an international approach of the Organisation for Economic Co-operation and Development. As the study focused on patients with recurrent CDI, the observed study population was categorized into (a) patients with CDI but without CDI recurrence (case group), (b) patients with CDI recurrence (recurrence group), and (c) patients without CDI (control group)., Results: Overall, 430 hospitalized patients from 12 European countries were included into the analysis between July 2018 and November 2018. Distribution of mean hospital length of stay and mean overall costs per patient between the case group, recurrence group, and control group were as follows: 22 days (95% CI 17-27 days) vs. 55 days (95% CI 17-94 days) vs. 26 days (95% CI 22-31 days; p 0.008) and € 15 242 (95% CI 10 593-19 891) vs. € 52 024 (95% CI 715-103 334) vs. € 21 759 (95% CI 16 484-27 035; p 0.010), respectively. The CDI recurrence rate during the observational period was 18%. Change escalation in CDI medication (OR 3.735) and treatment in an intensive care unit (OR 5.454) were found to be the most important variables associated with increased overall costs of patients with CDI., Conclusions: Treatment of patients with recurrent CDI results in a significant burden. Prevention of CDI recurrences should be in focus of daily patient care to identify the most cost-effective treatment strategy., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.)

BackgroundThere is a paucity of data on community-based Clostridioides difficile infection (CDI) and how these compare with inpatient CDI.AimTo compare data on the populations with CDI in hospitals vs the community across 12 European countries.MethodsFor this point-prevalence study (July-November 2018), testing sites sent residual diagnostic material on sampling days to a coordinating laboratory for CDI testing and PCR ribotyping (n = 3,163). Information on whether CDI testing was requested at the original site was used to identify undiagnosed CDI. We used medical records to identify differences between healthcare settings in patient demographics and risk factors for detection of C. difficile with or without free toxin.ResultsThe CDI positivity rate was 4.4% (country range: 0-16.2) in hospital samples, and 1.3% (country range: 0-2.2%) in community samples. The highest prevalence of toxinotype IIIb (027, 181 and 176) was seen in eastern European countries (56%; 43/77), the region with the lowest testing rate (58%; 164/281). Different predisposing risk factors were observed (use of broad-spectrum penicillins in the community (OR: 8.09 (1.9-35.6), p = 0.01); fluoroquinolones/cephalosporins in hospitals (OR: 2.2 (1.2-4.3), p = 0.01; OR: 2.0 (1.1-3.7), p = 0.02)). Half of community CDI cases were undetected because of absence of clinical suspicion, accounting for three times more undiagnosed adults in the community compared with hospitals (ca 111,000 vs 37,000 cases/year in Europe).ConclusionThese findings support recommendations for improving diagnosis in patients presenting with diarrhoea in the community, to guide good practice to limit the spread of CDI.

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.

Background: Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown., Methods: Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage., Results: Sequenced isolates (n = 624) were from 19 countries. Five ribotypes had within-country clustering: ribotype 356, only in Italy; ribotype 018, predominantly in Italy; ribotype 176, with distinct Czech and German clades; ribotype 001/072, including distinct German, Slovakian, and Spanish clades; and ribotype 027, with multiple predominantly country-specific clades including in Hungary, Italy, Germany, Romania, and Poland. By contrast, we found no within-country clustering for ribotypes 078, 015, 002, 014, and 020, consistent with a Europe-wide distribution. Fluoroquinolone resistance was significantly more common in within-country clustered ribotypes (P = .009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P < .001)., Conclusions: Two distinct patterns of C. difficile ribotype spread were observed, consistent with either predominantly healthcare-associated acquisition or Europe-wide dissemination via other routes/sources, for example, the food chain.

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics. While commercially available tests are being developed, potential surrogate antibiotics may be used as marker of susceptibility. Using tedizolid as an example of a new antibiotic, this special report makes recommendations to optimize routine susceptibility reporting.

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe., (This article is copyright of The Authors, 2016.)

Suboptimal laboratory diagnostics for Clostridium difficile infection (CDI) impedes its surveillance and control across Europe. We evaluated changes in local laboratory CDI diagnostics and changes in national diagnostic and typing capacity for CDI during the European C. difficile Infection Surveillance Network (ECDIS-Net) project, through cross-sectional surveys in 33 European countries in 2011 and 2014. In 2011, 126 (61%) of a convenience sample of 206 laboratories in 31 countries completed a survey on local diagnostics. In 2014, 84 (67%) of these 126 laboratories in 26 countries completed a follow-up survey. Among laboratories that participated in both surveys, use of CDI diagnostics deemed 'optimal' or 'acceptable' increased from 19% to 46% and from 10% to 15%, respectively (p  < 0.001). The survey of national capacity was completed by national coordinators of 31 and 32 countries in 2011 and 2014, respectively. Capacity for any C. difficile typing method increased from 22/31 countries in 2011 to 26/32 countries in 2014; for PCR ribotyping from 20/31 countries to 23/32 countries, and specifically for capillary PCR ribotyping from 7/31 countries to 16/32 countries. While our study indicates improved diagnostic capability and national capacity for capillary PCR ribotyping across European laboratories between 2011 and 2014, increased use of 'optimal' diagnostics should be promoted., (This article is copyright of The Authors, 2016.)

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol., (This article is copyright of The Authors, 2016.)

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile., (This article is copyright of The Authors, 2016.)

Background: Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe., Methods: We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012-13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched., Findings: During the study period, participating hospitals reported a mean of 65·8 tests (country range 4·6-223·3) for C difficile infection per 10 000 patient-bed days and a mean of 7·0 cases (country range 0·7-28·7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011-12 to 205 (48%) of 428 in 2012-13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory) were not diagnosed by participating hospitals because of an absence of clinical suspicion, equating to about 74 missed diagnoses per day., Interpretation: A wide variety of testing strategies for C difficile infection are used across Europe. Absence of clinical suspicion and suboptimum laboratory diagnostic methods mean that an estimated 40 000 inpatients with C difficile infection are potentially undiagnosed every year in 482 European hospitals., Funding: Astellas Pharmaceuticals Europe., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: In November 2008, a study was performed with support from the European Centre for Disease Prevention and Control (ECDC) to obtain an overview of Clostridium difficile infections (CDIs) in European hospitals. A collection of 398 C. difficile isolates obtained from this hospital-based survey was utilized to identify antimicrobial susceptibility patterns of common C. difficile PCR ribotypes across Europe., Methods: The MICs of three approved therapeutic agents (vancomycin, metronidazole and fidaxomicin) and LFF571 (a novel semi-synthetic thiopeptide antibiotic) were determined by the agar dilution method., Results: MICs of fidaxomicin and LFF571 were in general 2-4-fold lower than those of vancomycin and metronidazole. Isolates belonging to clade 2, including the hypervirulent ribotype 027, had one-dilution higher MIC50 and MIC90 values for fidaxomicin and metronidazole, whereas similar MIC values were observed for vancomycin and LFF571. Isolates belonging to C. difficile PCR ribotype 001 were more susceptible to fidaxomicin than other frequently found PCR ribotypes 014/020 and 078. Six isolates from three different countries had a metronidazole MIC of 2 mg/L. Four of the six isolates were characterized as PCR ribotype 001., Conclusions: There was no evidence of in vitro resistance of C. difficile to any of the four agents tested. However, the results suggest type-specific differences in susceptibility for the treatment agents we investigated. Continuous surveillance of C. difficile isolates in Europe is needed to determine the possible clinical implications of ribotype-specific changes in susceptibility to therapeutic agents.