Clinical characteristics and risk factors for Clostridioides difficile infection in the hematopoietic cell transplantation population

Background: Recipients of hematopoietic cell transplantation (HCT) are at increased risk for Clostridioides difficile infection (CDI) and its recurrence, which are associated with significant morbidity. We aimed to characterize risk factors for primary and recurrent CDI in a large cohort of HCT recipients. Methods: We conducted a retrospective cohort study of 2725 adults who underwent HCT from 2010–2023 to evaluate the epidemiology, timing, and risk factors for CDI. We compared patients who developed CDI with those who did not, adjusting for patient demographics, comorbidities, transplant factors, medications, and laboratory values. Among patients who developed CDI, we investigated risk factors for recurrent CDI. Results: The cumulative 1-year incidence of CDI was 17.8% among allogeneic HCT recipients (181/1016) and 4.1% among autologous recipients (71/1709). Overall CDI incidence increased by 1.4% annually during the study period (95%CI: 1.24–1.53%). Independent risk factors for primary CDI included penicillin antibiotics (aOR 1.51; 95%CI: 1.13–2.02), prior chemotherapy (aOR 8.36; 95%CI: 2.95–23.69 for 1–3 regimens), and umbilical cord blood stem cells (aOR 1.95; 95%CI: 1.07–3.57). Autologous HCT was associated with decreased risk. Among 252 patients with primary CDI, 22 (8.7%) developed recurrence. Macrolide use before index CDI (aOR 7.25; 95%CI: 1.80–29.2) and allogeneic HCT (aOR 31.04; 95%CI: 1.37–731.58) were associated with recurrence. Conclusion: CDI is a common, early complication of HCT particularly among allogeneic recipients. Penicillin exposure, prior chemotherapy, and cord blood stem cell source are key risk factors, while macrolide use is associated with recurrence. Our findings highlight potential targets for risk-stratified prevention strategies.