Clostridioides difficile Among Asymptomatic Onco-Hematological Carriers: Risk Factors, Molecular Characterization, and Antibiotic Resistance.

Background/Objectives:Clostridioides difficile colonization is common among hospitalized onco-hematological patients, yet its clinical significance and risk factors in this population remain incompletely characterized. This study aimed to determine the prevalence, risk factors, and genomic characteristics of C. difficile colonization among oncology and hematology inpatients, and to assess its relationship with progression to symptomatic infection. Methods: We conducted a prospective cohort study of patients admitted to the oncology and hematology departments of a tertiary-care hospital in the Canary Islands, Spain, between March and October 2025. Weekly active screening for C. difficile colonization was performed on stool samples throughout hospitalization. Risk factors were assessed using multivariable logistic regression, and whole-genome sequencing was performed on 16 of the 23 recovered isolates (after excluding 3 non-recoverable and 4 contaminated isolates) to characterize sequence types, ribotypes, and antimicrobial resistance determinants. Results: Among 215 patients (262 admission episodes), colonization was detected in 23 episodes (8.8%), with higher rates in oncology (10.9%) than hematology (7.2%; adjusted OR 0.37, 95% CI 0.14-0.96, p = 0.042). Chemotherapy administered during hospitalization was the strongest independent risk factor for colonization (adjusted OR 4.16, 95% CI 1.56-11.10, p = 0.004). Only 4.3% of colonizations were classified as truly community-associated, with 95.7% of patients showing documented healthcare contact. Sequencing of 16 isolates identified nine sequence types, including ST11 (ribotype 078, of zoonotic origin) and rare ribotypes (RT010, RT451); four isolates (36%) exhibited moxifloxacin resistance linked to gyrA/gyrB mutations, while all remained susceptible to vancomycin and metronidazole. No colonized patient progressed to symptomatic infection; the single CDI case in the cohort occurred in a non-colonized patient. Conclusions: These findings support current recommendations against isolating or treating asymptomatically colonized patients, while underscoring the need for continued genomic surveillance and reinforced environmental hygiene and antimicrobial stewardship in this high-risk population.