Clostridioides difficile Colonization and Infection in Pediatric Oncology and Stem Cell Transplant Patients

Background Pediatric oncology and hematopoietic stem cell transplant (HSCT) patients have elevated risk for Clostridioides difficile infection (CDI) which can prolong hospitalization and delay chemotherapy. Colonization is an important prelude to symptomatic CDI. We sought to characterize colonization status in these patients. Methods We retrospectively studied 276 stools longitudinally collected over 34 months from 32 HSCT and 12 oncology patients treated at a single tertiary center. Specimens were cultured for C. difficile and compared by whole genome sequencing (WGS). The fecal microbiome was characterized using 16S rRNA gene sequencing. Results Baseline cultures were positive in 16 (50%) HSCT and 2 (12%) oncology patients. On subsequent samples, 64% of patients initially negative acquired colonization, 8/15 (53%) HSCT patients and 8/10 (80%) oncology patients. Nine clonal strains and 25 multilocus sequence type (MLST) sequence types were identified by WGS, with 4 clones found in both cohorts. Nine patients had different strains at different timepoints. Seven clonal strains were found in multiple patients. Seven (15.9%) patients had symptomatic CDI. C. difficile-positive stools had greater microbial diversity than negative stools (Simpson Diversity Index =0.07, 95%CI 0.01-0.14, p=0.03, and 0.15, 95%CI 0.07-0.24, p<0.001) in oncology and HSCT cohorts, respectively. Conclusions C. difficile acquisition and colonization is common in pediatric oncology and HSCT patients. The high prevalence of clonally related strains in multiple patients suggests that asymptomatic patients may be important reservoirs of this pathogen, and lead to symptomatic CDI in some patients. Gut microbial composition may influence the risk of colonization.