Perform 2-step testing using GDH EIA or PCR (NAAT) combined with Toxin EIA:
- If results are discordant (one positive, one negative), send a cytotoxicity assay to Labcorp or Quest for confirmation.
Only Toxin B is considered toxigenic.
Define severe disease if WBC > 15 or creatinine > 1.5.

First-line therapy:
- Fidaxomicin 200 mg twice daily for 10 days (preferred due to lower recurrence rates compared to vancomycin).
- Vancomycin 125 mg four times daily for 10 days.
If symptoms persist despite standard treatment, evaluate for post-infectious IBS, IBD, microscopic colitis, or other causes of diarrhea.

Antibiotic tapering or prolonged suppressive therapy may help reduce recurrence.
Consider bezlotoxumab (Zinplava):
- A monoclonal antibody that binds to C. difficile toxin B.
- FDA-approved for use within 6 months of infection.
- Administered as a single infusion (~$4,000), but contraindicated in patients with heart failure.
Fecal microbiota transplantation (FMT) options:
- Rebyota: A single 150 mL dose of full-spectrum fecal material, given via enema or via colonoscopy to the cecum. Ferring can also arrange a nurse-administered home procedure.
- Vowst: Oral capsules containing live fecal microbiota spores. Administer after a standard antibiotic course and bowel preparation with 10 oz of magnesium citrate. The patient takes 4 capsules daily for 3 days. Available only in two pharmacies globally (for now).

Diagnosed based on systemic symptoms and radiographic evidence of colon dilation >6 cm.
Diagnostic criteria (Jalan et al.):
- Radiographic colon dilation >6 cm AND:
- At least three of the following:
  - Fever >38°C
  - Heart rate >120 bpm
  - Neutrophilic leukocytosis >10,500/microL
  - Anemia
- At least one of the following:
  - Dehydration
  - Altered sensorium
  - Electrolyte disturbances
  - Hypotension