From vancomycin to fidaxomicin: shifting paradigms in clostridioides difficile management.

<title>Abstract</title> Introduction: Clostridioides difficile infection (CDI) is one of the leading causes of antibiotic-associated diarrhea and represents a major global public health concern. Its clinical relevance has increased due to rising incidence, greater disease gravity, high recurrence rates, and the emergence of hypervirulent strains, making CDI a persistent challenge in daily clinical practice. Objective: To provide an updated narrative review of the epidemiology, pathogenesis, diagnostic approaches, and current therapeutic strategies for Clostridioides difficile infection, with emphasis on key clinical challenges and practical considerations. Methods: A structured literature review was conducted using PubMed/MEDLINE, Scopus, and SciELO databases. DeCS/MeSH terms related to Clostridioides difficile, epidemiology, diagnosis, treatment, and prevention were combined using Boolean operators. Articles published in English and Spanish between 2020 and 2025 were included, prioritizing systematic reviews, meta-analyses, original studies, and clinical practice guidelines. The search was last updated in january 2026. Results: CDI pathogenesis is primarily mediated by toxins A and B, which induce epithelial damage and colonic inflammation. Advances in diagnostic tools, particularly nucleic acid amplification tests and multistep diagnostic algorithms, have improved detection rates; however, inappropriate use may lead to overdiagnosis. Oral vancomycin remains a cornerstone of therapy, while fidaxomicin, monoclonal antibodies, and fecal microbiota transplantation have shown efficacy in reducing recurrence in selected patients. Conclusions: Effective management of CDI requires an integrated approach combining accurate diagnosis, appropriate antimicrobial therapy, and sustained preventive strategies.