Real-World Study Looks at Use of Bezlotoxumab, FMT for CDI

Megan Brooks

February 23, 2023

Bezlotoxumab and fecal microbiota transplant (FMT) are similarly effective for preventing recurrent Clostridioides difficile infection (rCDI) but are "infrequently" used in real-world practice in Spain, a new study finds.

In line with prior studies, this Spanish study also found improvement in CDI recurrence rates when these therapies were administrated earlier in the course of disease (first episodes and/or first recurrences).

The study by Patricia Muñoz, MD, PhD, from General University Hospital Gregorio Marañón in Madrid, and colleagues was published in the February issue of Open Forum Infectious Diseases.

Both bezlotoxumab and FMT are recommended therapies that have been shown to reduce rates of rCDI. Bezlotoxumab was approved in Spain in 2018. Muñoz and colleagues say their hospital has significant experience with FMT, which is performed with lyophilized oral capsules.

From January 2018 to April 2021, there were 1377 episodes of CDI at their hospital, and only 117 (8.5%) of these episodes were treated with either bezlotoxumab or FMT.

Researchers had full information for 100 of these CDI episodes: 51 were treated with bezlotoxumab, and 49 were treated with FMT.

Bezlotoxumab was more often used for patients with immunosuppression (67%) and for first episodes or first recurrences (71%). FMT was used only for CDI recurrences.

Despite the different conditions of the patients, there were no significant differences between bezlotoxumab and FMT in preventing either early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). Early rCDI was defined as an episode that occurs within the first 8 weeks following treatment with either bezlotoxumab or FMT, whereas late rCDI was defined as an episode occurring from 8 weeks to 1 year following treatment.

At 1-year follow-up, there was a trend toward fewer late rCDI episodes with bezlotoxumab than with FMT. However, the investigators think this effect may be partially explained by the higher non-CDI-related mortality rate observed in the bezlotoxumab group at 1-year follow-up (27.5% vs 14.3%; P = .10). None of the deaths were related to bezlotoxumab.

In multivariate analysis, risk factors for CDI recurrence after bezlotoxumab or FMT were treatment of a second or further recurrence (odds ratio [OR], 2.90) and the use of systemic non-CDI antibiotics afterward (OR, 3.45).

The researchers say their findings are in line with those of previous studies and "emphasize the need for preventive strategies for rCDI, including a close and specific antimicrobial stewardship intervention to avoid the use of inadequate antibiotics in these patients."

Findings May Not Reflect US Practice

The US Food and Drug Administration (FDA) approved bezlotoxumab injection (Zinplava) in 2016 to reduce the recurrence of CDI in patients aged 18 and older.

The FDA approved the first fecal microbiota product to prevent recurrence of CDI in people aged 18 years and older in late 2022. The product, Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.

Reached for comment, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia Medical School in Norfolk, noted that while the findings from Spain are interesting, the results "likely don't reflect real-world use in the United States."

The low use of fecal transplant in Spain was somewhat "surprising because that's become pretty much the standard in the United States after multiple relapses or high-risk relapse," Johnson told Medscape Medical News.

However, the current scale of FMT use in the United States remains unclear.

modeling study estimated that 10% to 15% of CDI cases are multiple, recurrent cases, which would translate to as many as 48,000 FMTs in the United States annually. The model also found that for every 1.5 FMTs performed, one episode of CDI is prevented. Thus, the full use of FMT could prevent as many as 32,000 recurrences every year, the researchers concluded.

Additionally, a registry analysis found that 90% of patients treated with FMT recovered from CDI, with few serious adverse events.

And, in 2021, the American College of Gastroenterology issued new guidelines on the management of CDI that include roles for FMT, combination testing, and bezlotoxumab. Its recommendation of FMT for individuals with multiple, recurrent episodes may contribute to an increase in its use.

Also, in the United States, most FMTs are administered via colonoscopy, whereas in the study from Spain, FMT was administered using oral capsules. However, a recent study found no significant difference between FMT delivered by capsule or colonoscopy.

The low use of both FMT and bezlotoxumab in Spain may be a matter of cost, Johnson noted. However, costs "may be offset" by hospitals' willingness to pay for something that could potentially minimize readmission for a condition that may be categorized as a nosocomial infection.

The study by Muñoz and colleagues was partially funded by Fondo de Investigaciones Sanitarias, Merck & Co, and the European Regional Development Fund. Muñoz received support for attending meetings for Pfizer, Angellini, Gilead, and Mundipharma. Johnson has disclosed no relevant financial relationships.

Open Forum Infect Dis. Published online January 25, 2023. Full text

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