Abstract

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a few ‘epidemic’ strains in specific geographical regions. Here, through detailed analysis of 10330 publicly-available C. difficile genomes from strains isolated worldwide (spanning 270 multilocus sequence types (STs) across all known evolu-tionary clades), this study provides the first species-wide snapshot of AMR genomic epidemiology in C. difficile. Of the 10330 C. difficile genomes, 4532 (43.9%) in 89 STs across clades 1–5 carried at least one genotypic AMR determinant, with 901 genomes (8.7%) carrying AMR determinants for three or more antimicrobial classes (multidrug-resistant, MDR). No AMR genotype was identified in any strains belonging to the cryptic clades. C. difficile from Australia/New Zealand had the lowest AMR prevalence compared to strains from Asia, Europe and North America (P < 0.0001). Based on the phylogenetic clade, AMR prevalence was higher in clades 2 (84.3%), 4 (81.5%) and 5 (64.8%) compared to other clades (collectively 26.9%) (P < 0.0001). MDR prevalence was highest in clade 4 (61.6%) which was over three times higher than in clade 2, the clade with the second-highest MDR prevalence (18.3%). There was a strong association between specific AMR determinants and three major epidemic C. difficile STs: ST1 (clade 2) with fluoroquinolone resistance (mainly T82I substitution in GyrA) (P < 0.0001), ST11 (clade 5) with tetracycline resistance (various tet-family genes) (P < 0.0001) and ST37 (clade 4) with macrolide-lincosamide-streptogramin B (MLSB ) resistance (mainly ermB) (P < 0.0001) and MDR (P < 0.0001). A novel and previously overlooked tetM-positive transposon designated Tn6944 was identified, predominantly among clade 2 strains. This study provides a comprehensive review of AMR in the global C. difficile population which may aid in the early detection of drug-resistant C. difficile strains, and prevention of their dissemination worldwide.

RAS ID

40561

Document Type

Journal Article

Date of Publication

1-1-2021

Volume

7

Issue

11

Funding Information

The Raine Medical Research Foundation National Health and Medical Research Council

Mahidol Scholarship from Mahidol University, Thailand

PubMed ID

34793295

School

School of Medical and Health Sciences

Grant Number

NHMRC Number : APP1138257

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publisher

Microbiology Society

Comments

Imwattana, K., Rodríguez, C., Riley, T. V., & Knight, D. R. (2021). A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile. Microbiology Society, 7(11), 1-13.

https://doi.org/10.1099/mgen.0.000696

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Link to publisher version (DOI)

10.1099/mgen.0.000696