Reviewed by Jose Lucar, MD, FIDSA, The George Washington University
Recurrent Clostridioides difficile infections (CDI) are driven by both relapse with the same strain and reinfection with different strains. In a genomic surveillance study conducted in Minnesota, researchers analyzed samples from 306 patients who experienced multiple CDI episodes between 2019 and 2021. Whole-genome sequencing (WGS) was used to assess the genetic diversity of C. difficile strains across infection events.
The study found that 64.7% of patients (198 of 306) had repeated infections with the same strain type, even beyond the conventional 8-week recurrence window. Among the 306 patients with recurrent CDI, repeat infection with a genetically distinct C. difficile strain occurred in at least 93 of 218 patients (42.7%) who had two documented infections and 52 of 88 patients (59.1%) who had three or more infections. Interestingly, no significant correlation was observed between mutation accumulation and time between infections, although nearly half of same-strain pairs exhibited changes in mobile genetic elements, suggesting ongoing genomic evolution.
The use of WGS enabled strain typing and detection of genetic changes over time. However, several limitations should be noted. The study’s geographic scope (Minnesota) and reliance on available clinical samples may have excluded some recurrent cases. Additionally, no host or environmental factors influencing recurrent CDI were included in the analysis. Finally, the use of WGS on single colonies isolated from stool specimens prevented investigation of polyclonal CDI events.
These findings enhance the understanding of C. difficile pathogenesis and underscore the complex interplay between strain persistence, genetic variation, and reinfection in recurrent CDI.
Reference:
Evans D, Friedman B, Pung K, et al. Insights on recurrent and sequential Clostridioides difficile infections from genomic surveillance in Minnesota, USA, 2019-2021. J Infect Dis. Published online October 1, 2025. Doi:10.1093/infdis/jiaf505