Genomic Epidemiology of Clostridioides difficile Infection: A cgMLST Analysis

Abstract

Aim
To characterise the genomic epidemiology of Clostridioides difficile infection (CDI) at Letterkenny University Hospital (LUH) using core-genome Multi Locus Sequence Typing (cgMLST), quantify true nosocomial transmission, distinguish relapse from reinfection, and examine the relationship between CDI patterns and institutional antimicrobial consumption.

Methods
In 2023 and 2024, 1,510 and 1,754 stool samples were screened, respectively for suspected CDI. GDH screening was positive in 153 (10.1%) and 226 (12.9%) with toxin EIA detecting active toxin in 86 (56.2%) and 106 (46.9%), respectively. PCR identified toxin genes in a further 44 (65%) and 72 (60%) of toxin-negative GDH-positive samples. Of these, 117, toxin-positive isolates from 94 patients underwent whole-genome sequencing and cgMLST. Molecular clusters were defined as ≤2 allelic differences, and epidemiological linkage required shared ward location and overlapping admission periods. National antimicrobial-use deciles were reviewed for CDI-associated agents.

Results
cgMLST identified 28 sequence types, with ST11 predominating (19, 16.2%). Of 48 clusters, only one represented confirmed nosocomial transmission. Recurrent CDI occurred in 10 out of 94 (11%), with 90% representing molecular relapse. LUH ranked among the highest national consumers of CDI-associated antimicrobials.

Discussion
CDI at LUH is driven primarily by endogenous activation of community-acquired strains rather than hospital transmission. High-risk antimicrobial use is the key modifiable driver, highlighting the need for strengthened antimicrobial stewardship supported by ongoing WGS surveillance.