Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB30014 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014-2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.
| S-EPMC6502822 | biostudies-literature
Project description:Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario
| PRJEB28391 | ENA
Project description:Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.
| S-EPMC8754133 | biostudies-literature
Project description:BackgroundA zoonotic association has been suggested for several PCR ribotypes (RTs) of Clostridioides difficile. In central parts of Sweden, RT046 was found dominant in neonatal pigs at the same time as a RT046 hospital C. difficile infection (CDI) outbreak occurred in the southern parts of the country.ObjectiveTo detect possible transmission of RT046 between pig farms and human CDI cases in Sweden and investigate the diversity of RT046 in the pig population using whole genome sequencing (WGS).MethodsWGS was performed on 47 C. difficile isolates from pigs (n = 22), the farm environment (n = 7) and human cases of CDI (n = 18). Two different core genome multilocus sequencing typing (cgMLST) schemes were used together with a single nucleotide polymorphisms (SNP) analysis and the results were related to time and location of isolation of the isolates.ResultsThe pig isolates were closely related (≤6 cgMLST alleles differing in both cgMLST schemes) and conserved over time and were clearly separated from isolates from the human hospital outbreak (≥76 and ≥90 cgMLST alleles differing in the two cgMLST schemes). However, two human isolates were closely related to the pig isolates, suggesting possible transmission. The SNP analysis was not more discriminate than cgMLST.ConclusionNo general pattern suggesting zoonotic transmission was apparent between pigs and humans, although contrasting results from two isolates still make transmission possible. Our results support the need for high resolution WGS typing when investigating hospital and environmental transmission of C. difficile.
| S-EPMC7751860 | biostudies-literature
Project description:Whole-genome sequencing (WGS) is a highly sensitive method for identifying genetic relatedness and transmission of Clostridioides difficile strains. Previous studies suggest that as few as 3 core genome single-nucleotide variants (SNVs) discriminate between genetically distinct isolates. Because a single C. difficile colony is selected from culture for WGS, significant within-host genetic diversity could preclude identification of transmission events. To evaluate the likelihood of missed transmission events using WGS of single colonies from culture, we examined within-host genetic diversity among C. difficile isolates collected from children. We performed WGS using an Illumina MiSeq instrument on 8 C. difficile colonies randomly selected from each culture performed on stool collected from 10 children (8 children diagnosed with C. difficile infection and 2 children with asymptomatic carriage); 77/80 (96%) isolate sequences were successfully assembled. Among 8/10 (80%) children, all isolates were the same sequence type (ST). The other 2 children each had mixed infection with two STs, although one ST predominated. Among 9/10 (90%) children, isotypic isolates differed by ≤2 SNVs; an isotypic isolate in the remaining child differed by 3 to SNVs relative to the other isolates from that child. Overall, among the 77 isolates collected from 10 stool cultures, 74/77 (96%) were clonal (i.e., same ST and ≤2 core genome SNVs) to other isolates in stool culture. In summary, we identified rare C. difficile within-host genetic diversity in children, suggesting that WGS of a single colony from stool is likely to appropriately characterize isolate clonality and putative transmission events in the majority of cases.
| S-EPMC6711918 | biostudies-literature
Project description:BackgroundThe rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. However, C. difficile 027 infections have been rarely reported in Asia, particularly in China.ResultsIn this study, we identified a rare C. difficile bloodstream infection (BSI) from three isolates of a patient during repeated hospital admission. This finding triggered a retrospective epidemiological study to scan all cases and strains emerged from this ward during the past three years. Using medical personnel interviews, medical record reviews and the genomic epidemiology, two outbreaks in 2012 and 2013-2014 were identified. Through using whole genome sequencing, we succeeded to trace the origin of the BSI strain. Surprisingly, we found the genome sequences were similar to C. difficile 027 strain R20291, indicating the occurrence of a rare C. difficile 027 strain in China. Integrated epidemiological investigation and whole genome sequencing of all strains, we constructed a nosocomial transmission map of these two C. difficile 027 outbreaks and traced the origin of the infection.ConclusionsBy genome sequencing, spatio-temporal analysis and field epidemiology investigation, we can estimate their complex transform network and reveal the possible modes of transmission in this ward. Based on their genetic diversity, we can assume that the toilets, bathroom, and janitor's equipment room may be contaminated area, which may be suggested to improve infection control measures in the following health care.
| S-EPMC4942892 | biostudies-literature
Project description:Genomic analysis of a diverse collection of Clostridioides difficile ribotype 078 isolates from Ireland and 9 countries in Europe provided evidence for complex regional and international patterns of dissemination that are not restricted to humans. These isolates are associated with C. difficile colonization and clinical illness in humans and pigs.
| S-EPMC8386809 | biostudies-literature
Project description:Clostridium difficile infection (CDI) is increasingly recognized globally as a cause of significant morbidity and mortality. This study aimed to provide insight into the various dynamics of C. difficile transmission and infection in the hospital. We monitored the toxin and resistance profiles as well as evolutionary relationships of C. difficile strains to determine the epidemiology over time in a teaching hospital in Shanghai, China between May 2014 and August 2015. The CDI incidence of inpatients and outpatients were 67.7 cases and 0.3 cases per 100,000 patient-days, with a nosocomial patient-environment-patient transmission in May and June 2015. C. difficile genotype ST81, a clone with tcdA-negative and tcdB-positive, was not only the most common strain (30.8%, 28/91) but also had much higher resistance rates to clindamycin and moxifloxacin compared with non-ST81 genotypes. Hospitalized patients infected with ST81 genotypes were over 65 years of age and had more comorbidities, however patients infected with ST81 presented with less clinical symptoms than non-ST81 infected patients. This study provides initial epidemiological evidence that C. difficile ST81 is a successful epidemic genotype that deserves continuous surveillance in China.
| S-EPMC5575120 | biostudies-literature
Project description:Effect on gene transcript levels upon up- or down-regulation of two component system WalRK (Wal-ON and Wal-OFF)
2022-04-09 | GSE200346 | GEO
Project description:BackgroundThe key epidemiological drivers of Clostridioides difficile transmission are not well understood. We estimated epidemiological parameters to characterize variation in C. difficile transmission, while accounting for the imperfect nature of surveillance tests.MethodsWe conducted a retrospective analysis of C. difficile surveillance tests for patients admitted to a bone marrow transplant (BMT) unit or a solid tumor unit (STU) in a 565-bed tertiary hospital. We constructed a transmission model for estimating key parameters, including admission prevalence, transmission rate, and duration of colonization to understand the potential variation in C. difficile dynamics between these 2 units.ResultsA combined 2425 patients had 5491 admissions into 1 of the 2 units. A total of 3559 surveillance tests were collected from 1394 patients, with 11% of the surveillance tests being positive for C. difficile. We estimate that the transmission rate in the BMT unit was nearly 3-fold higher at 0.29 acquisitions per percentage colonized per 1000 days, compared to our estimate in the STU (0.10). Our model suggests that 20% of individuals admitted into either the STU or BMT unit were colonized with C. difficile at the time of admission. In contrast, the percentage of surveillance tests that were positive within 1 day of admission to either unit for C. difficile was 13.4%, with 15.4% in the STU and 11.6% in the BMT unit.ConclusionsAlthough prevalence was similar between the units, there were important differences in the rates of transmission and clearance. Influential factors may include antimicrobial exposure or other patient-care factors.
| S-EPMC7844587 | biostudies-literature