Examining Bezlotoxumab and Fecal Microbiota Transplantation for Clostridioides difficile

With newer modalities and therapies for Clostridioides difficile (CDI) coming online, there is a need for more studies and understanding where best applied in the clinical setting.

Real world application of the human monoclonal antibody bezlotoxumab (Zinplava), and the modality of fecal microbiota transplantation (FMT), has been limited to a few factors including treatment guidelines, therapy cost, and the availability of the modality.

Investigators wanted to explore using both to evaluate the efficaciousness of bezlotoxumab (BZX) and FMT in preventing early (within 8 weeks) and late (within 1 year) CDI recurrences (rCDI).

This was a retrospective study conducted in a Spanish university hospital from January 2018 to April 2021. All adult patients with confirmed CDI were prospectively included in a database. Patients who received BZX or FMT during this period were selected. A follow-up appointment of at least 8 weeks was required, so cases for which there were no follow-up data were excluded.

The study included 100 CDI episodes for analysis with 51 cases treated with bezlotoxumab, and 49 with FMT.

The study was published in the Open Forum Infectious Diseases.

What the Data Shows
The monoclonal antibody was primarily used in immunosuppressed patients (66.7%) and in first episodes or first recurrences (70.6%). FMT was prescribed only in CDI recurrences.

bezlotoxumab. In October 2016, bezlotoxumab was FDA approved and indicated for treatment against C difficile toxin B, for the prevention of CDI recurrence. In this study, the therapy was administered on first episodes in 35.3%, on first recurrences in 35.3%, and on second or further recurrences in 29.4% according to the investigators. Of these, 45.0% of the CDI episodes were clinically severe.

Regarding the outcome, there were 10 (19.6%) early recurrences within 8 weeks and 5 (9.8%) late CDI episodes within 1 year of follow-up. The mortality rate was 7.8% in the first 8-week period and 27.5% in the 1-year follow-up period. None of the deaths were CDI related.

FMT. At this hospital where the study was conducted, FMT had been performed with lyophilized oral capsules. Patients received a single dose of FMT after completing a course of oral vancomycin or fidaxomicin for the treatment of a CDI episode. Selection of treatment in each case was decided according to local guidelines and per the advice of infectious diseases specialists and pharmacy department according to the investigators.

“Despite the different conditions of the patients, there were no significant differences between BZX and FMT in preventing early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). In the multivariate analysis, risk factors for recurrence were presence of ≥2 previous rCDI episodes (odds ratio [OR], 2.90; 95% CI, 1.03–8.63) and use of non-CDI antibiotics (OR, 3.45; 95% CI, 1.24–9.57),” they wrote.

“Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations.”

In terms of limitations, the investigators noted a few things including that this was a retrospective study, the heterogeneity of patients, and a small number of patients. Nonetheless, they did point out this has been one of the largest studies to compare these treatment approaches. 

The investigators noted a few conclusions from their study. “BZX and FMT were infrequently used in real-world practice (8.5% in our series) and in very different clinical scenarios, as BZX was more frequently assigned to patients with immunosuppression and for first and severe episodes, while FMT was indicated in cases with several prior CDI recurrences. Second, despite these differences, both strategies of treatment had equivalent effectiveness, assessed in terms of early and late rCDI episodes. Third, BZX and FMT appeared to be more effective in the treatment of first recurrences compared with second or further rCDI episodes.”