Clostridioides difficileWhole-genome Sequencing Differentiates Relapse With the Same Strain From Reinfection With a New Strain

Abstract

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 ≤2 allelic differences based on standard infection prevention and control assessment revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having reinfection based on timing of recurrence, 3 had isolates with ≤2 allelic differences between them suggesting relapse, with 2 having isolates differing by >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.

High Prevalence of Genetically Related Clostridium Difficile Strains at a Single Hemato-Oncology Ward Over 10 Years

“…In 29 patients multiple infections were caused by a relapse of the original strain, and in 12 patients were caused by the newly acquired strains. Based on the infecting strain genotyping ( Cho et al, 2020 ), the recurrent episode of infection in the latter 12 patients could be classified as a reinfection. The reinfection which occurred beyond 8 weeks of the initial infection was caused by the original strain ( Supplementary Table S2 ).…”

“…Although there are no definitive criteria for definition of relatedness ( Cho et al, 2020 ), genetic heterogeneity of C. difficile can be analyzed by a number of typing methods, which can be divided into band-based and sequence-based approaches ( Mancini et al, 2018 ). The most commonly used band-based approach is the PCR ribotyping.…”

“…However, WGS-based typing of C. difficile , based on single nucleotide variants (SNVs) and on allelic profiling of core genome genes, named core genome MLST (cgMLST), is still hampered by the lack of standardized nomenclature ( Bletz et al, 2018 ). Despite this, using WGS of C. difficile seems to be of practical importance in clinical settings as exemplified by several reports ( Griffiths et al, 2010 ; Bletz et al, 2018 ; Kociolek et al, 2018 ; Mancini et al, 2018 ; Michael Dunne et al, 2018 ; Pightling et al, 2018 ; Aoki et al, 2019 ; Berger et al, 2019 ; Janezic and Rupnik, 2019 ; Kong et al, 2019 ; Cho et al, 2020 ). As recently reported, WGS better differentiates C. difficile relapse from reinfection than do definitions based on timing of recurrence ( Cho et al, 2020 ).…”

Whole genome sequencing evidences higher rates of relapse inClostridioides difficileinfection caused by PCR ribotype 106

“…Current definitions are based only on the lapse since previous episode (8 or less weeks), but there are “late” recurrences (more than 8 weeks) that might be caused by the same strain, highlighting the need to change the standard definition of relapse. Additionally, as other authors have considered, to differentiate between relapses and reinfections might be important for controlling CDI, either through interventions to manage C. difficile transmission, or implementing treatment policies requiring a different handling or even individualized therapeutic strategies [29].…”

From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

“…In many cases, recurrence is attributed to infection with a different strain from the primary strain, suggesting continued microbiota perturbation following clearance, which allows for reinfection (18). However, most patients who relapse suffer from an infection with the same strain that caused the original episode (19,20). Novel strategies for predicting and limiting recurrent infections are key for the future treatment of C. difficile.…”