Non-Fecal Microbiota Transplantation Strategies for Treatment of Recurrent Clostridioides difficile Infection

Clostridioides difficile infection (CDI) is a leading healthcare-associated illness with significant recurrence rates and clinical burden. Recurrent CDI (rCDI) arises from microbiota disruption, often exacerbated by antibiotic therapy. Current treatment strategies include fidaxomicin and vancomycin taper regimens, with adjunctive options such as rifaximin in select cases. Preventive approaches focus on environmental decontamination and microbiome preservation. Emerging therapies, including live biotherapeutics, non-toxigenic strains, and microbiome-protective agents, show promise in reducing recurrence. Dietary interventions that enhance microbial diversity may also support recovery. Together, these strategies highlight a shift toward microbiome-centered management of rCDI.