Clostridioides difficile Whole Genome Sequencing Differentiates Relapse with the Same Strain from Reinfection with a New Strain

BACKGROUND: Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. METHODS: We recruited 468 subjects with C. difficile infection at Mayo Clinic Rochester between May and December 2016 and performed whole genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of recurrence of infection. Sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and predicted ribotype. RESULTS: There was no correlation between C. difficile isolates based on cgMLST or ribotype groupings and CDI outcome. Epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with 50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having reinfection based on timing of recurrence, 3 had isolates with 50 allelic differences - suggesting reinfection. CONCLUSIONS: Our findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on timing of recurrence.