What is the optimal treatment for an adult with pseudomembranous colitis (inflammation of the colon) caused by Clostridioides difficile (C. difficile) infection, presenting with diarrhea, abdominal pain, and high fever, after long-term antibiotic use?

Optimal Treatment for Pseudomembranous Colitis

Stop the inciting antibiotic immediately and start oral vancomycin 125 mg four times daily for 10 days, or oral fidaxomicin 200 mg twice daily for 10 days as first-line therapy. 1, 2

Immediate Management Steps

Discontinue the Inciting Antibiotic

• Stopping the causative antibiotic is essential and must be done as soon as possible, as continued use significantly decreases clinical response rates and increases recurrence risk 1
• This step alone may influence outcomes even before specific C. difficile treatment begins 1

Initiate Specific Antibiotic Therapy

For this patient presenting with severe disease (high fever, abdominal pain, diarrhea):

• Oral vancomycin 125 mg four times daily for 10 days is the preferred first-line treatment 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an equally effective alternative with lower recurrence rates 1, 2
• Vancomycin demonstrated superior cure rates compared to metronidazole in severe CDI (97% vs. 76%) 1, 2

Why Not Metronidazole?

Metronidazole should NOT be used as first-line therapy for this patient:

• The 2018 IDSA/SHEA guidelines explicitly state that vancomycin or fidaxomicin are recommended OVER metronidazole for initial episodes 1
• Metronidazole is now limited only to settings where access to vancomycin or fidaxomicin is unavailable 1, 2
• Repeated or prolonged metronidazole courses carry risk of cumulative and potentially irreversible neurotoxicity 1, 2
• Multiple randomized trials since 2000 have shown vancomycin superiority over metronidazole, particularly in severe disease 1

Disease Severity Assessment

This patient likely has severe CDI based on:

• High fever (systemic toxicity indicator) 1
• Severe abdominal pain 1
• Pseudomembranous colitis on endoscopy (if performed) 1

Severe disease is formally defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 2

Critical Management Principles

Avoid Harmful Interventions

• Do not use antimotility agents or opiates as they can precipitate toxic megacolon and worsen outcomes 1, 2
• Avoid proton pump inhibitors if not absolutely necessary 1

Monitoring Response

• Clinical response typically requires 3-5 days after starting therapy 1, 2
• Resolution of diarrhea may take 4-6 days based on clinical trial data 3
• Do not perform "test of cure" after treatment completion 1, 2

If Fulminant Disease Develops

If the patient deteriorates with hypotension, shock, ileus, or megacolon:

• Increase vancomycin to 500 mg orally four times daily 1
• Add IV metronidazole 500 mg every 8 hours (especially if ileus present) 1
• Consider vancomycin retention enemas 500 mg in 100 mL saline every 6 hours if ileus prevents oral delivery 1
• Urgent surgical consultation for possible subtotal colectomy 1

Recurrence Risk

• Approximately 20-25% of patients experience recurrence after initial treatment 2, 3
• For first recurrence, fidaxomicin is preferred 2
• For multiple recurrences, consider tapered/pulsed vancomycin regimen or fecal microbiota transplantation 1, 2

Common Pitfalls to Avoid

• Do not delay treatment while awaiting test results if clinical suspicion is high 1
• Do not use metronidazole as first-line therapy in 2025 - this represents outdated practice 1, 2
• Do not continue the inciting antibiotic even if treating another infection; switch to agents less associated with CDI if continued antimicrobial therapy is required 1
• Do not use IV vancomycin - it is not effective for CDI and must be given orally 3