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

EUCLID Study Group

Research output: Contribution to journalArticle

Abstract

Background Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown. Methods Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage. Results 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 =.009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P <.001). Conclusions 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, for example, the food chain.

Original languageEnglish
Pages (from-to)1035-1044
Number of pages10
JournalClinical Infectious Diseases
Volume67
Issue number7
DOIs
Publication statusPublished - Sep 14 2018
Externally publishedYes

Fingerprint

Ribotyping
Clostridium difficile
Italy
Cluster Analysis
Fluoroquinolones
Clostridium Infections
Romania
Food Chain
Hungary
Poland
Phylogeny
Single Nucleotide Polymorphism
Germany

Keywords

  • Clostridium difficile
  • community
  • healthcare
  • transmission
  • whole genome sequencing

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread. / EUCLID Study Group.

In: Clinical Infectious Diseases, Vol. 67, No. 7, 14.09.2018, p. 1035-1044.

Research output: Contribution to journalArticle

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title = "Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread",
abstract = "Background Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown. Methods Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage. Results 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 =.009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P <.001). Conclusions 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, for example, the food chain.",
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author = "{EUCLID Study Group} and Eyre, {David W.} and Davies, {Kerrie A.} and Georgina Davis and Fawley, {Warren N.} and Dingle, {Kate E.} and {De Maio}, Nicola and Andreas Karas and Crook, {Derrick W.} and Peto, {Tim E.A.} and Walker, {A. Sarah} and Wilcox, {Mark H.} and Longshaw, {Christopher M.} and Ed Kuijper and {Von Muller}, Lutz and Outi Lyytikainen and Silja Mentula and Fidelma Fitzpatrick and Emilio Bouza and Frederic Barbut and Monica Oleastro and Michel Delmee and Paola Mastrantonio and Torbjorn Noren and Franz Allerberger and Hanna Pituch and Maja Rupnik and Zsuzsanna Barna and Efthymia Petinaki and Otakar Nyč and Daniela Lemeni and Kate Ivanova and Elena Novakova",
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T1 - Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread

AU - EUCLID Study Group

AU - Eyre, David W.

AU - Davies, Kerrie A.

AU - Davis, Georgina

AU - Fawley, Warren N.

AU - Dingle, Kate E.

AU - De Maio, Nicola

AU - Karas, Andreas

AU - Crook, Derrick W.

AU - Peto, Tim E.A.

AU - Walker, A. Sarah

AU - Wilcox, Mark H.

AU - Longshaw, Christopher M.

AU - Kuijper, Ed

AU - Von Muller, Lutz

AU - Lyytikainen, Outi

AU - Mentula, Silja

AU - Fitzpatrick, Fidelma

AU - Bouza, Emilio

AU - Barbut, Frederic

AU - Oleastro, Monica

AU - Delmee, Michel

AU - Mastrantonio, Paola

AU - Noren, Torbjorn

AU - Allerberger, Franz

AU - Pituch, Hanna

AU - Rupnik, Maja

AU - Barna, Zsuzsanna

AU - Petinaki, Efthymia

AU - Nyč, Otakar

AU - Lemeni, Daniela

AU - Ivanova, Kate

AU - Novakova, Elena

PY - 2018/9/14

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N2 - Background Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown. Methods Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage. Results 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 =.009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P <.001). Conclusions 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, for example, the food chain.

AB - Background Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown. Methods Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage. Results 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 =.009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P <.001). Conclusions 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, for example, the food chain.

KW - Clostridium difficile

KW - community

KW - healthcare

KW - transmission

KW - whole genome sequencing

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