The antibiotic most commonly linked to the development of pseudomembranous colitis caused by Clostridioides difficile is Clindamycin.

Pseudomembranous colitis is an inflammation of the colon associated with overgrowth of Clostridioides difficile, a gram-positive, spore-forming anaerobic bacterium. This condition typically arises after disruption of the normal colonic flora, which allows C. difficile to proliferate and produce toxins that damage the colonic mucosa.

Certain antibiotics, especially those with broad-spectrum activity, are more likely to disturb the gut microbiota and predispose patients to C. difficile infection (CDI). Among the antibiotics listed:

- Clindamycin is historically the most notorious for causing CDI because it has a strong impact on anaerobic bacteria in the gut, which normally suppress C. difficile growth.

- Ampicillin can also cause some disruption but is less commonly implicated.

- Ciprofloxacin and other fluoroquinolones have been associated with outbreaks of hypervirulent C. difficile strains but are generally less strongly linked compared to clindamycin in classic teaching.

- Azithromycin, a macrolide, has a lower risk for CDI.

Key points:
- Clindamycin significantly disrupts normal gut flora, increasing susceptibility to CDI.
- Broad-spectrum antibiotics that affect anaerobic bacteria contribute the most to pseudomembranous colitis.
- The overgrowth of C. difficile leads to toxin-mediated colonic mucosal injury and pseudomembrane formation.

Reference: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th Edition, Volume 2, Chapter 147 - Clostridioides difficile Infection