Clostridioides difficile is well-known for its potential to cause healthcare-associated diarrhea in patients with previous antibiotic use. However, C. difficile can also be found as an asymptomatic... Show moreClostridioides difficile is well-known for its potential to cause healthcare-associated diarrhea in patients with previous antibiotic use. However, C. difficile can also be found as an asymptomatic colonizer of the gut. This thesis focuses on C. difficile colonization with the aim to better understand this condition and its role in epidemioloy of C. difficile infections. Investigations included microbiota analyses and transmission analyses. Show less
Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and this combination is reported to result in poorer survival compared with cancer alone. This study aimed to... Show morePatients with cancer have an increased risk of developing venous thromboembolism (VTE), and this combination is reported to result in poorer survival compared with cancer alone. This study aimed to investigate the impact of VTE on the survival of patients with cancer in a general population. The Scandinavian Thrombosis and Cancer (STAC) cohort, a population-based cohort including 144 952 participants without previous VTE or cancer, was used. During follow-up, cancer and VTE incidences were registered. "Cancer-related VTE" was defined as VTE diagnosed in patients with overt or occult cancer. The survival of participants without cancer and/or VTE ("disease-free") was compared with the survival of participants with cancer and cancer-related VTE. Cox regression models with cancer and VTE as time-varying exposures were performed to calculate hazard ratios for death. Subanalyses were performed across cancer types and stages and VTE type (deep vein thrombosis or pulmonary embolism). During follow-up (mean, 11.7 years), 14 621 participants developed cancer, and 2444 developed VTE, of which 1241 were cancer-related. The mortality rates (per 100 person years) for disease-free participants, VTE only, cancer only, and cancer-related VTE were 0.63, 5.0, 9.2, and 45.3, respectively. Compared with patients with cancer only, the risk of death for patients with cancer-related VTE was increased 3.4-fold. Within all cancer types, the occurrence of VTE increased the mortality risk 2.8-to 14.7-fold. In a general population, patients with cancer with VTE had a 3.4-fold higher mortality risk than patients with cancer without VTE, independent of cancer type. Show less
Objectives: To assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting.Methods: A multi-centre study was conducted at four... Show moreObjectives: To assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting.Methods: A multi-centre study was conducted at four hospitals located across the Netherlands. Newly admitted patients were screened for CDC. The risk of development of Clostridioides difficile infection (CDI) during admission and 1-year follow-up was assessed in patients with and without colonization. C. difficile isolates from patients with colonization were compared with isolates from incident CDI cases using core genome multi-locus sequence typing to determine whether onwards transmission had occurred.Results: CDC was present in 108 of 2211 admissions (4.9%), whereas colonization with a toxigenic strain (toxigenic Clostridoides difficile colonization [tCDC]) was present in 68 of 2211 admissions (3.1%). Among these 108 patients with colonization, diverse PCR ribotypes were found and no 'hypervirulent' PCR ribotype 027 (RT027) was detected (95% CI, 0-0.028). None of the patients with colonization developed CDI during admission (0/49; 95% CI, 0-0.073) or 1-year follow-up (0/38; 95% CI, 0-0.93). Core genome multi-locus sequence typing identified six clusters with genetically related isolates from patients with tCDC and CDI; however, in these clusters, only one possible transmission event from a patient with tCDC to a patient with CDI was identified based on epidemiological data.Conclusion: In this endemic setting with a low prevalence of 'hypervirulent' strains, screening for CDC at admission did not detect any patients with CDC who progressed to symptomatic CDI and detected only one possible transmission event from a patient with colonization to a patient with CDI. Thus, screening for CDC at admission is not useful in this setting. Monique J.T. Crobach, Clin Microbiol Infect 2023;29:891 & COPY; 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
A subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential... Show moreA subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential importance, C. difficile plasmids remain poorly characterized. Here, we provide the complete genome sequence of a human clinical isolate that carries three high-copy number plasmids from three different plasmid families that are therefore compatible. For two of these, we identify a region capable of sustaining plasmid replication in C. difficile that is also compatible with the plasmid pCD630 that is found in many laboratory strains. Together, our data advance our understanding of C. difficile plasmid biology. Show less
Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility... Show moreGut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p < 0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients' gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile. Show less
Objectives: Clostridium difficile is a major global human pathogen divided into five clades, of which Glade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains.... Show moreObjectives: Clostridium difficile is a major global human pathogen divided into five clades, of which Glade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterize this Glade.Methods: In this cohort study the clinical presentation of C. difficile RT023 infections was analysed in comparison with known 'hypervirulent' and non-hypervirulent strains, using data from the Netherlands national C. difficile surveillance programme. European RT023 strains of diverse origin were collected and whole-genome sequenced to determine the genetic similarity between isolates. Distinctive features were investigated and characterized.Results: Clinical presentation of C. difficile RT023 infections show severe infections akin to those seen with 'hypervirulent' strains from clades 2 (RT027) and 5 (RT078) (35%, 29% and 27% severe CDI, respectively), particularly with significantly more bloody diarrhoea than RT078 and non-hypervirulent strains (RT023 8%, other RTs 4%, p 0.036). The full genome sequence of strain CD305 is presented as a robust reference. Phylogenetic comparison of CD305 and a further 79 previously uncharacterized European RT023 strains of diverse origin revealed minor genetic divergence with >99.8% pairwise identity between strains. Analyses revealed distinctive features among Glade 3 strains, including conserved pathogenicity locus, binary toxin and phage insertion toxin genotypes, glycosylation of S-layer proteins, presence of the RT078 four-gene trehalose cluster and an esculinase-negative genotype.Conclusions: Given their recent emergence, virulence and genomic characteristics, the surveillance of Glade 3 strains should be more highly prioritized. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Background. Clostridioides difficile infection (CDI) is increasingly reported in the community. The aim of this study was to analyze characteristics of hospitalized patients with community-onset... Show moreBackground. Clostridioides difficile infection (CDI) is increasingly reported in the community. The aim of this study was to analyze characteristics of hospitalized patients with community-onset CDI (CO-CDI).Methods. In the Netherlands, 24 hospitals (university-affiliated and general hospitals) participate in the sentinel CDI surveillance program. Clinical characteristics and 30-day outcomes of hospitalized patients >2 years old diagnosed with CDI are registered. Samples of these patients are sent to the national reference laboratory for polymerase chain reaction ribotyping. Data obtained for this surveillance from May 2012 to May 2018 were used to compare CO-CDI with hospital-onset (HO)-CDI episodes.Results. Of 5405 registered cases, 2834 (52.4%) were reported as HO-CDI, 2174 (40.2%) were CO-CDI, and 339 (6.3%) had onset of symptoms in another healthcare facility (eg, nursing home). The proportion of CO-CDI increased over the years and was lower during winter months. Hospitalized patients with CO-CDI were younger (63.8 vs 68.0 years, P < .001) and more often females (53.0% vs 49.6%, P = .02) than patients with HO-CDI. Median time between onset of symptoms and CDI testing was longer in CO-CDI (4 vs 1 day, P < .001). Similar ribotypes were found in CO-CDI and HO-CDI, but ribotype 001 was more frequent among HO-CDI, whereas ribotype 023 was more frequent in CO-CDI. Six of 7 (85.7%) surgeries due to CDI, 27 of 50 (54%) ICU admissions due to CDI, and 48 of 107 (44.9%) of CDI-associated deaths were attributable to CO-CDI.Conclusions. Our study demonstrates that patients hospitalized with CO-CDI contribute substantially to the total number of CDI episodes and CDI-associated complications in hospitals, stressing the need for awareness and early testing for CDI in community and outpatient settings and also in patients admitted from community with diarrhoea. Surveillance programs that also target nonhospitalized CDI patients are needed to understand the true burden and dynamics of CDI. Show less
The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case-control study, we compared the risk... Show moreThe purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case-control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high. Show less
