Whole-genome characteristics of isolates from recurrent Clostridioides difficile infections

Clostridioides difficile infection (CDI) imposes considerable medical and economic burdens on patients and healthcare systems due to its high recurrence rate and treatment refractoriness. Recurrent CDI (rCDI) may result from a relapse of the same strain or reinfection by a different strain. However, the genetic and evolutionary features of strains causing rCDI remain poorly understood. Therefore, in this study, CDI strains were collected from patients with ≥2 clinically defined infections. Through antimicrobial susceptibility testing and whole-genome sequencing (WGS), we investigated the correlation between relapse and reinfection strains. WGS revealed that 40 of 82 patients with CDI (48.8%) relapsed with the original strain, including 6 cases exceeding the 8-week recurrence interval definition. The recurrence interval was significantly shorter for relapse cases than for reinfections. Moreover, the relapse rate was significantly higher in hospital-associated (HA-CDI) cases than in community-associated (CA-CDI) cases (P < 0.05). Notably, strains isolated from relapse cases showed a trend toward higher resistance rates to clindamycin, imipenem, moxifloxacin, and tigecycline than those from reinfection cases. No significant genomic differences, including resistance genes, virulence genes, and transposons, were observed between relapse and reinfection strains. Core genome evolutionary analyses indicated that both types were predominantly under purifying selection, with only a few genes related to transcriptional regulation and energy metabolism under positive selection. The findings indicate that relapse and reinfection strains share similar evolutionary drivers, suggesting that recurrence may be more closely associated with other factors, such as host gut microbiota or gene expression regulation.

Clostridioides difficile infection (CDI) poses a major challenge in healthcare settings due to its high recurrence rate. Accurate differentiation between relapse of the original strain and reinfection with a new strain is crucial for effective management of recurrent Clostridioides difficile infection (rCDI). This study combined whole-genome sequencing (WGS) and antimicrobial susceptibility testing to thoroughly examine the genomic characteristics of isolates from rCDI patients at our hospital, aiming to identify potential genomic features and key factors contributing to rCDI. Core genome analysis revealed highly consistent evolutionary trajectories between recurrent and reinfection strains, with no significant differences in their genetic lineages. This finding suggests that recurrence tendencies may be influenced more by host-specific factors or regulatory adaptations. These insights offer a new direction for developing targeted management strategies for rCDI.