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

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.

Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center. METHODS: This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression. RESULTS: One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence. CONCLUSIONS: Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.