European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults

SCOPE: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as fecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS: Key questions on CDI treatment were formulated by the guideline committee and included: what is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI; what is the best treatment when no oral therapy is possible; can prognostic factors identify patients at risk for severe and recurrent CDI; and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence, and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS: Important changes compared with previous guideline include but are not limited to: (1) metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, (2) fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, (3) FMT or bezlotoxumab in addition to Standard of Care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, (4) bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and (5) bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.