Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in C. difficile, including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact.
Keywords: Clostridium difficile; antimicrobial resistance; biofilm; efflux pumps; plasmids; reduced susceptibility; van genes.