Assessment of rifaximin and rifampicin resistance across Clostridioides difficile ribotypes: a systematic review and meta-analysis

Clostridioides difficile is an opportunistic pathogen of the gastrointestinal tract that can cause illnesses ranging from diarrhea to pseudomembranous colitis. Recurrent Clostridioides difficile infection remains a major clinical challenge, with substantial relapse rates after standard antibiotic therapy. Emerging evidence suggests that rifaximin can be used after the conventional therapy to reduce risk of the recurrence. However, rifaximin resistance in Clostridioides difficile remains the primary concern. The aim of this systematic review and meta-analysis is to estimate the risk of rifaximin resistance in Clostridioides difficile infection and among different ribotypes. The search included PubMed, Scopus, Web of Science, and Cochrane Library for studies reporting rifaximin resistance in Clostridioides difficile isolates. After systematically screening 731 records from all databases and excluding 664 studies, a total of 67 studies were included in the meta-analysis. The findings of the meta-analaysis indicated a resistance rate of 15.1% (95% CI, 12.0%-18.9%) for rifaximin and/or rifampicin and 12.8% (95% CI, 8.8%-18.2%) for rifaximin alone. Ribotype-specific analysis revealed high rifaximin resistance in RT017 (72.3%), RT027 (47.0%), and RT018 (20.9%), while RT012, RT002, RT112, and RT014/020 demonstrated low resistance. The study finding indicate that rifaximin/rifamycin resistance in Clostridioides difficile is concerning and not randomly distributed but is more frequently associated with certain ribotypes.