Abstract

BackgroundPediatric oncology and hematopoietic stem cell transplant patients (POTP) are at increased risk for Clostridioides difficile infection (CDI) and recurrence. It is unknown whether recurrent CDI is related to the same C. difficile strain as the initial CDI. We describe genomic relatedness of C. difficile strains in patients with multiple CDI using whole-genome sequencing (WGS).MethodsThis was a retrospective cohort study of CDI in POTP in 2016. CDI cases were identified by electronic medical record search for positive C. difficile toxin PCR tests. Patients with multiple CDI episodes were identified. CDI episodes were classified as incident, duplicate or recurrent using National Healthcare Safety Network (NHSN) definitions. Retrieved residual stool specimens were cultured anaerobically, toxin-producing C. difficile isolates were determined using a cell culture cytotoxicity assay with neutralization and WGS was performed followed by core genome MLST (cgMLST). Variability of the isolates was summarized by strain type (ST), and a minimum spanning tree was constructed, defining genomically related isolates as those with <7 allele difference.ResultsEighteen patients had 51 positive C. difficile samples. CDI were classified as incident in 31 (61%) episodes, recurrent in 18 (36%), and duplicate in 2 (3%). Isolates from 47 (92%) samples were sequenced, identifying 14 different strain types (ST) in 41 (87%) isolates. Of the 31 incident CDI, 13 (42%) episodes occurred 8 weeks or more after the initial incident CDI. Among those 13 incident CDI, 7 (54%) had prior CDI due to a related isolate. Of the 18 recurrent CDIs, 10 (55%) were due to an isolate related to the previous incident CDI and 5 (28%) were due to an isolate unrelated to the incident CDI. The relatedness of the remaining 3 recurrent episodes could not be evaluated because no isolate was available for sequence analysis.ConclusionCDI classification of incident vs. recurrent infection using NHSN definition might be not applicable in POTP. WGS showed that more than half of CDI episodes classified as incident were actually a recurrence of a previous C. difficile strain. Similarly, some CDI episodes classified as recurrent were actually re-infection with a different stain.DisclosuresRandall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board

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