Molecular Epidemiology and Genetic Relatedness of Clostridioides difficile Isolates in Pediatric Oncology and Transplant Patients Using Whole Genome Sequencing

Whole genome sequencing (WGS) identified a highly diverse group of Clostridioides difficile isolates among pediatric oncology and transplant patients with C. difficile infection (CDI). Classification of recurrent and incident CDI by WGS can differ from that by clinical surveillance criteria. Background The incidence of Clostridioides difficile infection (CDI) has been rising among hospitalized children, with poor understanding of genomic variability of C. difficile isolates in this population. Methods This was a retrospective cohort study of CDI in inpatient and outpatient pediatric oncology and cell transplant patients (POTPs) in 2016 and 2017. CDI cases were identified by positive C. difficile toxin polymerase chain reaction tests. Retrieved residual stool specimens were cultured anaerobically and toxin-producing C. difficile isolates underwent whole genome sequencing (WGS) followed by core genome multilocus sequence typing. Plausible time and location epidemiologic links among the closely related strains were evaluated to identify potential transmission events. Results Among 226 CDI episodes in 157 patients, 202 stool samples were cultured and had positive cytotoxicity tests. Sequencing identified 33 different strain types in 162 (80%) isolates. Thirty-nine (28%) patients had multiple episodes of CDI, and 31 clusters of related isolates were identified, 15 (47%) of which involved exclusively multiple specimens from the same patient. For the 16 clusters involving multiple patients, epidemiologic investigation revealed only 2 (12.5%) clusters with potential transmission events. Conclusions WGS identified a highly diverse group of C. difficile isolates among POTPs with CDI. Although WGS identified clusters of closely related isolates in multiple patients, epidemiologic investigation of shared inpatient exposures identified potential transmission in only 2 clusters. Clostridioides difficile transmission was uncommon in this population. More than 70% of new CDI reinfections in POTPs are actually recurrences caused by a previous CDI strain.