Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread
<strong>Background</strong> Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype is however unknown. <strong>Methods</strong> Inpatient diarrhoeal faecal samples submitted on o...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Oxford University Press
2018
|
| _version_ | 1797084757622784000 |
|---|---|
| author | Eyre, D Davies, K Davis, G Fawley, W Dingle, K De Maio, N Karas, A Crook, D Peto, T Walker, A Wilcox, M |
| author_facet | Eyre, D Davies, K Davis, G Fawley, W Dingle, K De Maio, N Karas, A Crook, D Peto, T Walker, A Wilcox, M |
| author_sort | Eyre, D |
| collection | OXFORD |
| description | <strong>Background</strong> Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype is however unknown. <strong>Methods</strong> Inpatient diarrhoeal faecal samples submitted on one day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates ribotyped; those from the 10 most prevalent ribotypes were Illumina whole-genome sequenced. Pairwise single nucleotide differences (SNPs) were obtained from recombination-corrected maximum-likelihood phylogenies. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median SNPs between isolates within versus across different countries using permutation tests. Time-scaled Bayesian phylogenies where used to reconstruct the historic location of each lineage. <strong>Results</strong> 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=0.009). Fluoroquinolone-resistant isolates were also more tightly geographically clustered, median (IQR) 43 (0-213) miles between each isolate and the most closely genetically-related isolate vs. 421 (204-680) in non-resistant pairs (p<0.001). <strong>Conclusions</strong> 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, e.g. the food chain. |
| first_indexed | 2024-03-07T01:59:30Z |
| format | Journal article |
| id | oxford-uuid:9cdd003c-ab15-483e-9b52-9cdef6ae1000 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:59:30Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:9cdd003c-ab15-483e-9b52-9cdef6ae10002022-03-27T00:39:08ZTwo distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spreadJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9cdd003c-ab15-483e-9b52-9cdef6ae1000Symplectic Elements at OxfordOxford University Press2018Eyre, DDavies, KDavis, GFawley, WDingle, KDe Maio, NKaras, ACrook, DPeto, TWalker, AWilcox, M<strong>Background</strong> Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype is however unknown. <strong>Methods</strong> Inpatient diarrhoeal faecal samples submitted on one day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates ribotyped; those from the 10 most prevalent ribotypes were Illumina whole-genome sequenced. Pairwise single nucleotide differences (SNPs) were obtained from recombination-corrected maximum-likelihood phylogenies. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median SNPs between isolates within versus across different countries using permutation tests. Time-scaled Bayesian phylogenies where used to reconstruct the historic location of each lineage. <strong>Results</strong> 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=0.009). Fluoroquinolone-resistant isolates were also more tightly geographically clustered, median (IQR) 43 (0-213) miles between each isolate and the most closely genetically-related isolate vs. 421 (204-680) in non-resistant pairs (p<0.001). <strong>Conclusions</strong> 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, e.g. the food chain. |
| spellingShingle | Eyre, D Davies, K Davis, G Fawley, W Dingle, K De Maio, N Karas, A Crook, D Peto, T Walker, A Wilcox, M Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title | Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title_full | Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title_fullStr | Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title_full_unstemmed | Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title_short | Two distinct patterns of Clostridium difficile diversity across Europe indicates contrasting routes of spread |
| title_sort | two distinct patterns of clostridium difficile diversity across europe indicates contrasting routes of spread |
| work_keys_str_mv | AT eyred twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT daviesk twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT davisg twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT fawleyw twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT dinglek twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT demaion twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT karasa twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT crookd twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT petot twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT walkera twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread AT wilcoxm twodistinctpatternsofclostridiumdifficilediversityacrosseuropeindicatescontrastingroutesofspread |