Abstract / Summary
Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated diarrhea and is being increasingly recognized in community settings. The management of CDI is complicated by diagnostic uncertainty, recurrent disease, and uneven access to newer therapies. Clinicians must distinguish infection from colonization, individualize therapy selection, and anticipate barriers to recurrence prevention. This narrative review examines diagnostic and therapeutic barriers in adult CDI care, with particular emphasis on the U.S. healthcare, regulatory, and reimbursement setting. Several guidelines prefer fidaxomicin for an initial nonfulminant CDI episode when available. Oral vancomycin is an effective alternative, and metronidazole is reserved for initial nonsevere CDI when preferred agents are unavailable. Antibiotic options for recurrent CDI include standard or extended-pulsed fidaxomicin and standard-course or tapered-and-pulsed vancomycin regimens. After antibacterial treatment, conventional fecal microbiota transplantation (FMT) and two FDA-approved microbiota products, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), may be used in appropriately selected patients to prevent another recurrence. In ECOSPOR III, recurrence through 8 weeks was 12.4% of VOS recipients and 39.8% of placebo recipients. In PUNCH CD3, Bayesian model–estimated treatment success through 8 weeks was 70.6% with RBL and 57.5% with placebo. Because the trials used different populations, endpoints, definitions, and analytical frameworks, these figures should not be interpreted as a head-to-head comparison. The discontinuation of bezlotoxumab in the United States and reduced availability of stool bank-derived FMT have further constrained recurrence prevention options. Practical considerations include diagnostic stewardship, assessment of recurrence risk, and timely access to indicated recurrence prevention therapy.