Yes! Clindamycin has historically been the #1 Step 1 association, but in real clinical practice, fluoroquinolones (especially ciprofloxacin) are now among the most common culprits, and broad-spectrum cephalosporins and ampicillin are also high on the list.

The mechanism is ecological: these antibiotics wipe out the normal colonic flora (especially Bacteroides and other anaerobes that compete with C. diff). This opens a niche for C. difficile spores — which are resistant to alcohol hand gel and most disinfectants — to germinate and colonize the colon. Then they produce Toxins A and B.

Treatment: vancomycin PO (oral, not IV — needs to reach the colon) or fidaxomicin for initial episodes. Recurrent C. diff → consider fecal microbiota transplant (FMT).