Available online 20 September 2022, 102638

Spores are a current yet challenging target.

Antibiotic resistance urges the development of new antimicrobial therapies.

Specialized metabolites from gut microbiota are a valuable source of new molecules.

Genetic engineering and nanotechnology are promissory areas.

Designing effective microbial consortia is crucial against C. difficile infections.

Clostridioides difficile infection (CDI) is a significant worry within healthcare institutions and the community. It is one of the leading agents causing severe diarrhea worldwide. Effective management is critical since the morbidity and mortality attributed to CDI have increased exponentially over the past 20 years. Currently, antibiotics are the standard treatment for primary C. difficile infection, but at the same time, they are associated with disease relapse and increased drug resistance. CDI's high recurrence rates, spore generation, and antimicrobial resistance are currently significant challenges that urge the development of new options to combat this infection. This review describes up-and-coming alternatives and how they can mitigate the challenges associated with CDI. Here we have discussed the advantages and challenges of current and experimental alternatives against CDI.

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