Mechanisms and impact of antimicrobial resistance in Clostridioides difficile.

The evolution of antimicrobial resistance in Clostridioides difficile has markedly shaped its epidemiology and detrimentally impacted patient care. C. difficile exhibits resistance to multiple classes of antimicrobials, due to accumulation of horizontally acquired resistance genes and de novo mutations to drug targets. Particularly worrying is that declines in clinical success of firstline CDI antimicrobials coincide with the spread of strains that are more resistant to these drugs. Yet, there is still much to learn regarding the prevalence of genetic elements in clinical isolates, their molecular mechanisms, and the extent to which this information can be translated to develop molecular diagnostics that improve antimicrobial prescribing and antimicrobial stewardship approaches for CDI. Thus, this perspective discusses current understanding and knowledge gaps of antimicrobial resistance mechanisms in C. difficile, emphasizing on CDI therapies.