Bezlotoxumab is used to reduce recurrent Clostridioides difficile infection, although heart failure (HF) worsening has been reported in prior trials. A retrospective cohort analysis published in Infectious Disease Reports evaluated the incidence and predictors of heart failure (HF) exacerbations among adults treated with bezlotoxumab for Clostridioides difficile infection. 

Data were obtained from the TriNetX research network and included U.S. adults who received bezlotoxumab. Patients were stratified into three predefined groups based on baseline HF status: no HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). The primary outcomes were 90-day HF events and all-cause mortality. Cox proportional hazards models were used to identify independent predictors of HF exacerbations.

A total of 2,515 patients were included, of whom 89% had no prior HF, 4% had HFpEF, and 7% had HFrEF. The 90-day incidence of HF events differed significantly across groups, occurring in 1% of patients without HF, 29% of those with HFpEF, and 52% of those with HFrEF (P<0.001). Overall, 90-day all-cause mortality was 0.9%, with subgroup-specific rates of 0.04% (no HF), 4% (HFpEF), and 11% (HFrEF) (P<0.001).

In adjusted analyses, HFrEF (adjusted hazard ratio [aHR] 19.400) and HFpEF (aHR 8.632) were strong predictors of HF events. Additional risk factors included heart transplant (aHR 7.485), hyperlipidemia (aHR 3.184), valvular heart disease (aHR 2.267), chronic kidney disease stage ≥3 (aHR 1.715), and ischemic heart disease (aHR 1.987), while non-cardiac solid organ transplant was associated with lower risk (aHR 0.333).

HF event rates were higher among bezlotoxumab recipients with pre-existing HF, particularly HFrEF, indicating differing risk according to baseline cardiac status.