The pathogenesis of Clostridioides difficile infection (CDI) involves several key steps:

1. Disruption of the normal colonic microflora, typically due to antibiotics , PPI, or, less commonly, chemotherapeutic agents. The most common Antibiotics associated with CDI and diarrhea include clindamycin, second- and third-generation cephalosporins, ampicillin, amoxicillin, and Even Vancomycin or Metronidazole, which were typically the treatment, can predispose C.Diff infection.  Being immunosuppressed or elderly age is linked to disruption of the colonic microbioma.
2. Oral ingestion of difficile or its spores, leading to colonization of the large intestine; production of toxins A and B, which are released into the colonic lumen; binding and internalization of these toxins by colonocytes and inflammatory cells in the lamina propria; and resulting colonic inflammation and tissue damage, manifesting as colitis. Being in hospital or nursing home is a risk factor for infection.
3. Host factors, especially the immune response to difficile toxins, play a critical role in determining whether a person remains an asymptomatic carrier or develops colitis. For example, in infants <2 years old, colonisation for C.diff is difficile varies from 25% to 80% because they have not yet developed a stable complex colonic microbiota thar prevents colonisation of pathogenic microorganisms (the reason they do not become infected is probably the lacking of toxin receptor expression on the immature colonic epithelium

As stated above, C. difficile produces two primary toxins: toxin A (TcdA), an enterotoxin, and toxin B (TcdB), a cytotoxin. Toxin A has a carbohydrate-binding site that aids in the intracellular transport of both toxins A and B. Once inside the cell, these toxins inactivate pathways mediated by the Rho family of proteins, leading to colonocyte damage, breakdown of intercellular tight junctions, and ultimately colitis. 

 C. difficile transferase (CDT; or binary toxin) is a third toxin produced by some C. difficile strains, including the epidemic PCR ribotypes 027. It probably can form microtubule-based protrusions on epithelial cells, which theoretically could have a clinical impact. There are reports of severe CDI development caused by the TcdA⁻TcdB⁻CDT⁺ strains.

The BI/NAP1/027 strain is hypervirulent and resistant to fluoroquinolones,  has intensive spore production, and is responsible for the most severe CDI cases.  This epidemic strain is characterized by two mutations in the toxin regulatory gene tcdC   causing increased production of toxins A and B, and has a higher risk of mortality or colectomy.

The incubation period before the symptoms can be up to a week, but usually around 48h.

Clinical manifestation can be from asymptomatic, to diarrhoea (usually watery stools with mucous but without blood).  Up to 10% of IBD patient may develop CDI , this higher risk is likely due to altered microbioma, mucosal damage and abnormal immune response, therefore any IBD flare up should always be tested for CDI.