This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.