Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread

Eyre, David W; Davies, Kelvin J.A.; Davis, Georgina; Fawley, Warren N.; Dingle, Kate E.; Maio, Nicola De; Karas, Andreas; Crook, Derrick W.; Peto, Tim E. A.; Walker, A. Sarah; Wilcox, Mark H.

doi:10.1093/cid/ciy252

Cited by 65 publications

(76 citation statements)

References 38 publications

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“…RT BI/NAP1/027, a common epidemic RT is found in the United States, Canada, Mexico, England, Denmark, Hungary, Italy, Germany, Serbia, Romania, and Poland. 105,109,110 RTs 591, 106, and 002 are the prevailing RTs in Colombia. 111 Antibiotic resistance is associated with outbreaks, nearly all strains of RTs, such as BI/NAP1/027, 001, and 106 are resistant to erythromycin, many are resistant to fluoroquinolones, and some strains of BI/NAP1/027 and 001 are resistant to clindamycin as well.…”

Section: Emerging Strains and Epidemic Ribotypesmentioning

confidence: 99%

Clostridium difficile Infection: An Epidemiology Update

Roo

Regenbogen

2020

Clinics in Colon and Rectal Surgery

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Clostridium (reclassified as “Clostridioides”) difficile infection (CDI) is a healthcare-associated infection and significant source of potentially preventable morbidity, recurrence, and death, particularly among hospitalized older adults. Additional risk factors include antibiotic use and severe underlying illness. The increasing prevalence of community-associated CDI is gaining recognition as a novel source of morbidity in previously healthy patients. Even after recovery from initial infection, patients remain at risk for recurrence or reinfection with a new strain. Some pharmaco-epidemiologic studies have suggested an increased risk associated with proton pump inhibitors and protective effect from statins, but these findings have not been uniformly reproduced in all studies. Certain ribotypes of C. difficile, including the BI/NAP1/027, 106, and 018, are associated with increased antibiotic resistance and potential for higher morbidity and mortality. CDI remains a high-morbidity healthcare-associated infection, and better understanding of ribotypes and medication risk factors could help to target treatment, particularly for patients with high recurrence risk.

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Section: Emerging Strains and Epidemic Ribotypesmentioning

confidence: 99%

Clostridium difficile Infection: An Epidemiology Update

Roo

Regenbogen

2020

Clinics in Colon and Rectal Surgery

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“…On the contrary, in a recent study performed in North Macedonia, around 48% of isolates belonged to 001/072 (17). As opposed to the ribotypes widely distributed across Europe, in a study performed in 2012-2013 including 482 European hospitals, some ribotypes had evidence of clear withincountry clustering: ribotype 356, found only in Italy; ribotype 018, predominantly isolated in Italy; and ribotype 176, with distinct Czech and German clades (18).…”

Section: Resultsmentioning

confidence: 72%

Clostridioides difficile ribotype distribution in a large teaching hospital in Serbia

Korać

Rupnik

Nikolić

et al. 2020

Preprint

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Background: The global epidemic of nosocomial diarrhea caused by Clostridioides (Clostridium) difficile started in 2000, with high mortality rates and emergence of a new hypervirulent strain NAP1/BI/027. The aim of this study was to assess the presence of ribotype 027 and other C. difficile ribotypes in a Serbian University Hospital, compare the temporal variability of ribotypes three years apart, as well as to compare clinical, demographic and laboratory characteristics and disease outcome among patients infected with 027 and non-027 ribotype. This was a prospective observational cohort study addressing four-month intervals during 2014/2015 and 2017/2018. Results: Ribotyping was performed in 64 non-duplicate C. difficile strains. Ribotype 027 was the most prevalent, and was detected in 53 (82.8%) patients (43/45 and 10/19 patients in 2014-2015 and 2017/2018, respectively). Other detected ribotypes were 001/072 in 4 (6,3%), 002 in 4 (6,3%), 014/020 in 2 (3,1%) and 176 in 1 (1,5%) patient. The percentage of the patients infected with ribotype 027 significantly decreased during the three-year period, from 95.6% to 52.6% (p<0.001). Ribotype 027 infection was associated with fluoroquinolone treatment more frequently than infection with other ribotypes [33 (62.3%) vs. 2 (18.2%), p= 0.010)]. A severe C. difficile infection was diagnosed more often in patients with the detected ribotype 027 compared to those infected with non-027 ribotypes (p=0.006). No significant difference in the mortality and recurrence rates was found between the patients infected with ribotype 027 and those infected with other ribotypes [10/53 (18.8%) vs. 2/11 (18.2%), p=0.708, and 10/35 (28.6%) vs. 0/2 (0%), p=1.000, respectively].Conclusion: C. difficile ribotype 027 was the most prevalent ribotype among patients in a large Serbian hospital, but there is a clear decreasing trend.

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“…Reads (without stringent quality trimming) were also mapped to the 630 reference genome as described previously (1,11,18), using stampy (19) for mapping and mpileup (20) for variant calling, followed by quality filtering of variants. Variant calls were required to have a quality score of Ն30, be homozygous under a diploid model, be supported by Ն5 high quality reads (including Ն1 read in each direction and a consensus of Ն90% of bases), and not be within a repetitive region of the genome.…”

Section: Methodsmentioning

confidence: 99%

Hash-Based Core Genome Multilocus Sequence Typing for Clostridium difficile

et al. 2019

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Pathogen whole-genome sequencing has huge potential as a tool to better understand infection transmission. However, rapidly identifying closely related genomes among a background of thousands of other genomes is challenging. Here, we describe a refinement to core genome multilocus sequence typing (cgMLST) in which alleles at each gene are reproducibly converted to a unique hash, or short string of letters (hash-cgMLST). This avoids the resource-intensive need for a single centralized database of sequentially numbered alleles. We test the reproducibility and discriminatory power of cgMLST/hash-cgMLST compared to those of mapping-based approaches in Clostridium difficile, using repeated sequencing of the same isolates (replicates) and data from consecutive infection isolates from six English hospitals. Hash-cgMLST provided the same results as standard cgMLST, with minimal performance penalty. Comparing 272 replicate sequence pairs using reference-based mapping, there were 0, 1, or 2 single-nucleotide polymorphisms (SNPs) between 262 (96%), 5 (2%), and 1 (<1%) of the pairs, respectively. Using hash-cgMLST, 218 (80%) of replicate pairs assembled with SPAdes had zero gene differences, and 31 (11%), 5 (2%), and 18 (7%) pairs had 1, 2, and >2 differences, respectively. False gene differences were clustered in specific genes and associated with fragmented assemblies, but were reduced using the SKESA assembler. Considering 412 pairs of infections with ≤2 SNPS, i.e., consistent with recent transmission, 376 (91%) had ≤2 gene differences and 16 (4%) had ≥4. Comparing a genome to 100,000 others took <1 min using hash-cgMLST. Hash-cgMLST is an effective surveillance tool for rapidly identifying clusters of related genomes. However, cgMLST/hash-cgMLST generate more false variants than mapping-based approaches. Follow-up mapping-based analyses are likely required to precisely define close genetic relationships.

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Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread

Cited by 65 publications

References 38 publications

Clostridium difficile Infection: An Epidemiology Update

Clostridium difficile Infection: An Epidemiology Update

Clostridioides difficile ribotype distribution in a large teaching hospital in Serbia

Hash-Based Core Genome Multilocus Sequence Typing for Clostridium difficile

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