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Clostridioides difficile is a Gram positive spore-forming rod and mainly responsible for nosocomial diarrhea in developed nations. Molecular and antimicrobial surveillance is important for monitoring the strain composition including genotypes of high epidemiological importance such as ribotype 027 (RT027) and corresponding resistance patterns. 1535 isolates obtained from samples sent between 2014 and 2019 to the German National Reference Center (NRC) for diagnostic reasons (NRC strain set), and 1143 isolates from a Tertiary Care University Center in Saarland, Germany (non-NRC strain set), were evaluated using antibiotic susceptibility testing and ribotyping. In the NRC strain set, RT027 overtook RT001, the main RT found in the preceding studies, and dominated with 36.2%, followed by RT001 (13.3%), and RT014 (8.5%). Of note, since 2016 a constant decrease of RT027 could be noticed. In the non-NRC strain set a large strain diversity was present with RT014 (18%) and RT001 (8.9%) being most prevalent. In NRC samples, resistance towards metronidazole, vancomycin, moxifloxacin, clarithromycin and rifampicin was 2.7%, 0%, 57.1%, 53.2% and 19.2%, respectively. Metronidazole resistance was almost exclusively found in RT027 isolates. Rifampicin resistance was also observed predominantly in isolates of RT027, constituting an almost four-fold increase, when compared to preceeding studies in this region. In conclusion these data demonstrate that RT027 is a driver for rifampicin and metronidazole resistance, underlining the importance of continuous surveillance efforts., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: There are inconsistent data on the risk factors for Clostridium difficile infection (CDI) in the literature. Aims: To use two C. difficile infection (CDI) case-control study groups to compare risk factors in hospitalized patients with diarrhea across different countries. Methods: A multi-center group of CDI cases/controls were identified by standardized testing from seven countries from the prior EUropean, multi-center, prospective bi-annual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhea (EUCLID). A second group of CDI cases/controls was identified from a single center in Germany [parallel study site (PSS)]. Data were extracted from the medical notes to assess CDI risk factors. Univariate analyses and multivariate logistic regression models were used to identify and compare risk factors between the two groups. Results: There were 253 and 158 cases and 921 and 584 controls in the PSS and EUCLID groups, respectively. Significant variables from univariate analyses in both groups were age ≥65, number of antibiotics (OR 1.2 for each additional antibiotic) and prior hospital admission (all p < 0.001). Congestive heart failure, diabetes, admission from assisted living or Emergency Department, proton pump inhibitors, and chronic renal disease were significant in PSS (all p < 0.05) but not EUCLID. Dementia and admitted with other bacterial diseases were significant in EUCLID ( p < 0.05) but not PSS. Following multivariate analyses, age ≥ 65, number of antibiotics and prior hospital admission were consistently identified as CDI risk factors in each individual group and combined datasets. Conclusion: Our results show that the same CDI risk factors were identified across datasets. These were age ≥ 65 years, antibiotic use and prior hospital admission. Importantly, the odds of developing CDI increases with each extra antibiotic prescribed., (Copyright © 2020 Davies, Lawrence, Berry, Davis, Yu, Cai, Gonzalez, Prantner, Kurcz, Macovei, Pituch, Nováková, Nyč, Gärtner, Berger, Oleastro, Cornely, Vehreschild, Pedneault and Wilcox.)

Background: Nosocomial Clostridioides difficile infection (CDI) complicates up to 1% of all hospital admissions and is associated with considerable health burden., Aims: To determine the incidence and outcomes of nosocomial CDI at a major University Medical Center., Methods: Consecutive adult nosocomial CDI cases were prospectively identified. Stool samples were collected for ribotyping and antibiotic resistance testing. Patients were followed for eight weeks after discharge for relapse., Results: Over a 2-year period, 215 patients developed nosocomial CDI (incidence 2:1000) and 200 (mean age 62.2±19.6 years) gave informed consent. Mean hospital stay was 23.3±28.9 days (range 0-278). Infection was diagnosed within 7 days of admission (range 0-95) in 129 patients (64.5%). More than two-thirds (69.0%) were previously hospitalized within 12 weeks of the index hospitalization. Twenty five percent received prior antibiotics within eight weeks. Fifty-two patients (26.0%) did not receive antibiotics prior to diagnosis. Considerable comorbidities (Charlson Comorbidity Index ≥8) were noted in 33.5% of patients. Recurrence occurred in 43 patients (21.5%). On multivariate logistic regression, fluoroquinolone exposure was the only predictor of recurrence (OR=2.9, 95%CI 1.1-7.7). Overall mortality was 14.0% and CCI ≥8 was the only predictor on multivariate analysis (p=0.004). Genotyping did not identify any known hypervirulent strains and all isolates were susceptible to metronidazole and vancomycin., Conclusion: Antibiotic exposure, comorbidities, and prior hospitalization constitute the major risk factors for nosocomial CDI. Recurrence is common and is associated with fluoroquinolones exposure. High baseline comorbidity score was the only predictor of increased mortality in this prospective cohort., (Copyright © 2019. Published by Elsevier Ltd.)

Reported rates of C. difficile infection (CDI) have increased in many settings; however, these can be affected by factors including testing density (test-density) and diagnostic methods. We aimed to describe the impact of multiple factors on CDI rates. Hospitals (n = 182) across five countries (France, Germany, Italy, Spain, and UK) provided data on; size and type of institution, CDI testing methodology, number of tests/month and patient-bed-days (pbds)/month over one year. Incidence rates were compared between countries, different sized institutions, types of institutions and testing method. After univariate analyses, the highest CDI rates were observed in Italy (average 11.8/10,000pbds/hospital/month), acute/primary hospitals (12.3/10,000pbds/hospital/month), small hospitals (16.7/10,000pbds/hospital/month), and hospitals using methods that do not detect toxin (NO-TOXIN) (e.g. GDH/NAAT or standalone NAAT) (10.7/10,000pbds/hospital/month). After adjusting for test-density, highest incidence rates were still in Italy, acute/primary hospitals and those using NO-TOXIN. The relative rate in long-term healthcare facilities (LTHCFs) increased, but size of institution no longer influenced the CDI rate. Test-density appears to have the largest effect on reported CDI rates. NO-TOXIN testing still influences CDI rates, even after adjusting for test-density, which is consistent with tests that 'overcall' true CDI. Low test-density can mask the true burden of CDI, e.g. in LTHCFs, highlighting the importance of good quality surveillance., Competing Interests: Declaration of competing interest KD has received honoraria from Astellas Pharma Europe, Cepheid Inc and Summit, and grant support from Astellas Pharma Europe, bioMerieux, Pfizer and Sanofi-Pasteur. GD has received grant support from Astellas Pharma Europe, bioMerieux, Pfizer and Sanofi-Pasteur. FB is advisory board member for and/or has received scientific grants from Merck, Cubist, Sanofi Pasteur, DaVolterra, Pfizer and Astellas. FB has received scientific grants from BioMérieux, Alere, Cubist, Astellas, bioMérieux, Orion diagnostica, Quidel-Bühlmann, Greiner, Mobidiag. CE has received conference funding from Alere and Astellas and honoraria from Astellas. NP has received honoraria as speaker for MSD, Pfizer, Astellas, Novartis, Angelini and received honoraria as member of scientific advisory board for MSD, Pfizer, Astellas, The Medicines Company, Zambon, Becton Dickinson, and Achaogen. MHW has received: consulting fees from Abbott Laboratories, Actelion, Astellas, Astra-Zeneca, Bayer, Biomèrieux, Cerexa, Cubist, Durata, The European Tissue Symposium, The Medicines Company, MedImmune, Merck, Motif Biosciences, Nabriva, Optimer, Paratek, Pfizer, Qiagen, Roche, Sanofi-Pasteur, Seres, Summit, and Synthetic Biologics; lecture fees from Abbott, Alere, Astellas, Astra-Zeneca, Merck, Pfizer & Roche; and grant support from Abbott, Actelion, Astellas, Biomèrieux, Cubist, Da Volterra, Sanofi-Pasteur, Seres, Summit and The European Tissue Symposium, Merck. FKB has received consultant fees from MSD. CD is an employee of Sanofi Pasteur. All other authors have no conflicts to declare. We would like to acknowledge all of our study sites and collaborators:, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Clostridium (Clostridioides) difficile is the main cause of nosocomial diarrhoea. Ribotype 018 (RT018) has been recognized as the predominant strain responsible for C. difficile infection (CDI) in Italy, whereas in most other European countries only sporadic RT018 cases occur. Between August and October 2015, a suspected C. difficile outbreak at two associated hospitals in Southern Germany was investigated by comprehensive molecular typing. Surprisingly, RT018 was detected in 9/82 CDI patients, which has never been described before in a German outbreak. Phenotypic analysis revealed fluoroquinolone and macrolide resistance. Genetic subtyping using multiple-locus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS) was performed and outbreak isolates were directly compared to sporadic German RT018 isolates and to epidemic ones from Milan, Northern Italy. Molecular typing confirmed a hospital outbreak with closely related RT018 isolates. Both, MLVA and WGS revealed high similarity of outbreak strains with epidemic isolates from Italy, but low similarity to other German isolates. Comparison between both typing strategies showed that ribotyping in combination with MLVA was appropriate to identify related isolates and clonal complexes, whereas WGS provided a better discrimination with more detailed information about the phylogenetic relationship of isolates. This is the first hospital outbreak in Germany presumably caused by cross-national transmission of an Italian epidemic RT018 strain., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area., (Copyright © 2018 Elsevier GmbH. All rights reserved.)