Insights on Recurrent and Sequential Clostridioides difficile Infections From Genomic Surveillance in Minnesota, USA, 2019-2021.

Abstract

The frequent temporal recurrence of Clostridioides difficile infection (CDI) may be the result of relapse with the same strain or reinfection with a different strain. We used whole-genome sequencing (WGS) to assess the genetic diversity and molecular evolution of strains that caused recurrent or sequential CDI. We analyzed data from active population- and laboratory-based surveillance of CDI in Minnesota, USA. We performed WGS on isolates collected from 306 patients with multiple CDI events during 2019-2021. We identified multi-locus sequence types (MLSTs), nucleotide variants, and putative mobile genetic elements (MGEs) from WGS data to study the genetic similarity and evolution of those C. difficile genomes. Among patients with multiple CDI events in the surveillance period, 198 (64.7%) had multiple infections of the same MLST, including 49.6% of patients with subsequent infections beyond the 8-week limit of the case definition for recurrent CDI Among 232 temporally defined events of recurrent CDI, 155 (66.8%) involved isolates of the same MLST. There were no statistically significant correlations between accumulated mutations and elapsed time between same-MLST CDI events. Analysis of sequential same-MLST C. difficile genomes showed evidence of gain or loss of putative mobile genetic elements (MGEs) in 45.6% of genome pairs. Leveraging the largest CDI genomic dataset to date, our results confirm prior findings that recurrent CDI is a combination of reinfection and/or change in the ascendant strain in mixed infection, and relapse, while expanding knowledge on the evolution of pathogenic C. difficile strains in the human gastrointestinal tract.