Follow your Gut: Microbiome-Based Approaches in the Developmental Pipeline for the Prevention and Adjunctive Treatment of Clostridioides difficile Infection (CDI)

Purpose of Review: Antibiotic use is the most important modifiable risk factor for the development of Clostridioides difficile infection (CDI). In addition, up to a quarter of patients treated with standard-of-care antibiotics experience disease recurrence. Until 2016, when bezlotoxumab was approved by the U.S. Food and Drug Administration (FDA), antibiotics were the only medication class approved for use in CDI. A growing knowledge of the roles that the gut microbiome and immune system play in CDI progression and recovery demands new approaches to treatment. As a result, there are many agents, including adjunctive biotherapeutics, nontoxigenic C. difficile competitors, enzymes, and antibiotic binders, used to prevent and treat CDI in the developmental pipeline. The purpose of this focused review is to summarize these unique therapies in all stages of development. Recent Findings: Here, we discuss 13 agents in development, including four that have completed phase II trials, four in phase II trials, three in phase I trials, and two still undergoing preclinical trials. A number of new approaches including adjunctive biotherapeutics (n = 7), nontoxigenic C. difficile competitors (n = 1), enzymes used to prevent gut dysbiosis (n = 4), and antibiotic binders (n = 1) are discussed here. Summary: The CDI therapeutic pipeline contains a variety of unique microbiome-based approaches targeting both prevention and adjunctive treatment of CDI. The future of CDI management promises a variety of innovative approaches to better manage this disease state.