TY - JOUR
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
Y1 - 2018/9/14
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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U2 - 10.1093/cid/ciy252
DO - 10.1093/cid/ciy252
M3 - Article
C2 - 29659747
AN - SCOPUS:85053899364
VL - 67
SP - 1035
EP - 1044
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 7
ER -