Clostridium difficile

**Microbiology:** Gram-positive, spore-forming, obligate anaerobic rod. Spores are resistant to heat, alcohol-based hand sanitizers, and acid, and spread by the fecal-oral route. Soap and water handwashing and sporicidal agents (bleach) are needed for decontamination. Now reclassified as Clostridioides difficile.

**Pathophysiology:** - Broad-spectrum antibiotics deplete normal colonic flora (colonization resistance), which allows C. difficile overgrowth. - Toxin A (TcdA) is an enterotoxin and toxin B (TcdB) is a cytotoxin. Both glucosylate Rho GTPases, which disrupts the actin cytoskeleton and causes epithelial cell death, inflammation, and neutrophil recruitment. - This produces pseudomembranes: yellow-white plaques of fibrin, neutrophils, and necrotic debris on the colonic mucosa. - Hypervirulent strain NAP1/BI/027 produces more toxin, has a binary toxin, and has a tcdC deletion. It is associated with fluoroquinolone resistance and severe disease.

**Risk factors:** Antibiotics (clindamycin, fluoroquinolones, cephalosporins, ampicillin/amoxicillin; any antibiotic is a risk), hospitalization or long-term care, age >65, PPIs (association), immunosuppression, IBD, and recent GI surgery.

**Clinical presentation:** Watery, foul-smelling diarrhea, abdominal pain or cramping, fever, and leukocytosis. Severe disease has WBC ≥15,000 or creatinine >1.5 mg/dL. Fulminant disease causes hypotension or shock, ileus, and megacolon. Ileus may mean diarrhea is absent. Complications include toxic megacolon, perforation, and sepsis. Recurrence occurs in about 20% of patients.

**Diagnosis:** - Test only symptomatic patients (≥3 unformed stools in 24 hours). - Stool testing is a two-step or multistep algorithm: GDH antigen plus toxin A/B enzyme immunoassay, with NAAT/PCR (toxin gene) as the arbiter or standalone test. PCR is sensitive but may detect colonization. - Do not do a test of cure. - Colonoscopy shows pseudomembranes but is rarely needed. - Culture is not used routinely.

**Treatment:** - Stop the inciting antibiotic if possible. - Initial episode: fidaxomicin 200 mg PO BID for 10 days (preferred, lower recurrence). Oral vancomycin 125 mg QID for 10 days is an acceptable alternative. Metronidazole is no longer first-line, and is used only for non-severe disease if the others are unavailable. - Fulminant: high-dose oral vancomycin (500 mg QID) plus IV metronidazole. Add rectal vancomycin if ileus is present. Surgery (subtotal colectomy) is for perforation or refractory disease. - Recurrence: fidaxomicin or a vancomycin taper/pulse. Bezlotoxumab (anti-toxin B monoclonal antibody) is an adjunct for recurrence but has been discontinued by the manufacturer. Fecal microbiota transplantation (FMT) or approved microbiome therapeutics (e.g., Rebyota, Vowst) are used for multiple recurrences. - Avoid antimotility agents in active severe disease.

**Prevention:** Contact (enteric) precautions with a private room, gloves and gown, soap and water handwashing, bleach-based environmental cleaning, and antibiotic stewardship.

**High-yield buzzwords:** Pseudomembranous colitis, "volcano" or "summit" lesions on histology, post-antibiotic diarrhea, Rho GTPase glucosylation, spore-forming, alcohol gel ineffective, FMT for recurrence.