*Purpose: Clostridioides difficile is an urgent health threat associated with significant morbidity and mortality. Recipients of solid organ (SOT) and hematopoietic-cell transplantations (HCT) are at high risk for Clostridioides difficile infection (CDI), particularly recurrent disease. Bezlotoxumab (BEZ) was approved in 2016 for prevention of CDI recurrence; however, insufficient data exists regarding its use among SOT and HCT recipients. We sought to evaluate the effectiveness of BEZ among transplant recipients at our institution.

*Methods: We performed a retrospective analysis at our institution comparing SOT or HCT recipients who received BEZ to historic controls without BEZ receipt between January 2017 and June 2019. Controls were matched 2:1 based on transplant receipt, prior CDI episodes and concomitant receipt of broad-spectrum antibiotics. Primary outcome was 90-day CDI recurrence. Secondary outcomes included hospital readmission, mortality, and safety.

*Results: Among 47 BEZ recipients, 27 (57%) were transplant recipients (89% SOT & 11% HCT). A total of 54 controls were identified for comparison, 67% SOT (p=0.03) and 33% HCT (p=0.03). Baseline characteristics were similar for BEZ and control groups: median Charlson Comorbidity Index score (IQR) 4 (2, 6) versus 4 (2, 6), median number of lifetime CDI episodes (IQR) 3 (1, 4) versus 3 (2, 4), presence of severe CDI 15% versus 32%, concomitant broad-spectrum antibiotic use 70% versus 67%, fecal transplant receipt 19% versus 9%, and extended duration of anti-CDI antibiotics beyond 14 days 82% versus 65% respectively. Oral vancomycin was the predominant anti-CDI treatment of choice, 89% for both groups. Recurrence of CDI at 90 days was 19% for BEZ and 30% for control (OR 0.54; 95% CI, 0.17-1.68, p=0.29). All-cause 90-day mortality and hospital readmission was not significantly different for BEZ and control groups, 0 versus 6% and 52% versus 63% respectively. For those with prior CDI history, 90-day recurrence was 24% BEZ vs. 45% controls (p=0.15). BEZ was well tolerated, and there were no heart failure exacerbations among BEZ recipients and 2 exacerbations identified from control group.

*Conclusions: BEZ use in high-risk transplant recipients was associated with a non-significant reduction in CDI recurrence at 90-days. Our analysis was limited by small numbers and significant number of both BEZ recipients and controls receiving extended duration of anti-CDI antibiotics, which could have contributed to inability to show a statistical difference in recurrence. Further studies are needed to determine the true impact of BEZ on prevention of recurrent CDI in this high-risk group of patients.

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