What is the treatment approach for an elderly or immunocompromised patient presenting with pseudomembranous colitis, likely caused by Clostridioides difficile (C. difficile), following antibiotic therapy?

Treatment for Pseudomembranous Colitis (Clostridioides difficile Infection)

Critical First Step: Discontinue Inciting Antibiotics

Immediately discontinue the causative antibiotic if clinically feasible, as continued antibiotic use significantly increases recurrence risk. 1, 2 If ongoing antibiotic therapy is medically necessary for another infection, switch to agents less frequently associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline. 1

Assess Disease Severity to Guide Treatment Selection

Disease severity classification is essential before selecting therapy:

Non-severe CDI is defined by: 2, 3

• Stool frequency <4 times daily
• White blood cell count ≤15,000 cells/mL
• Serum creatinine <1.5 mg/dL
• No signs of severe colitis

Severe CDI is characterized by one or more of: 2, 4

• White blood cell count ≥15,000 cells/mL
• Serum creatinine >1.5 mg/dL
• Temperature >38.5°C with rigors
• Hemodynamic instability or septic shock
• Signs of peritonitis (abdominal tenderness, rebound, guarding) or ileus
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Colonic wall thickening or distension on imaging

First-Line Antibiotic Treatment

For Both Non-Severe and Severe CDI:

Oral vancomycin 125 mg four times daily for 10 days is the first-line treatment. 2, 3 This represents a shift from older guidelines that recommended metronidazole for mild disease—vancomycin is now preferred across all severity levels based on superior efficacy. 2, 3

Fidaxomicin 200 mg orally twice daily for 10 days is an equally effective alternative and may be particularly beneficial for patients at high risk of recurrence (elderly patients with multiple comorbidities receiving concomitant antibiotics). 2, 5

Important Caveat About Metronidazole:

Metronidazole 500 mg orally three times daily for 10 days should only be used for initial episodes of non-severe CDI when access to vancomycin or fidaxomicin is limited. 1, 3 Metronidazole has inferior efficacy compared to vancomycin, particularly in severe disease, and repeated or prolonged courses must be avoided due to risk of cumulative and potentially irreversible neurotoxicity. 1, 3

Treatment for Fulminant/Complicated CDI

For patients with fulminant disease (hypotension, shock, ileus, or megacolon): 3

• Oral vancomycin 500 mg four times daily (higher dose than standard)
• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1, 3
• Consider intravenous metronidazole 500 mg three times daily as adjunctive therapy 1
• Obtain immediate surgical consultation if any of the following are present: colonic perforation, severe ileus, systemic inflammation with deteriorating clinical condition despite appropriate antibiotic therapy, or serum lactate exceeding 5.0 mmol/L 1, 2

Critical Supportive Measures

Avoid antiperistaltic agents (loperamide) and opiates, as they may precipitate toxic megacolon and worsen outcomes. 1, 3, 4

Discontinue proton pump inhibitors if not medically necessary, though evidence for this intervention remains limited. 1, 4

Monitoring Treatment Response

Expected clinical response includes decreased stool frequency or improved consistency within 3 days, with no new signs of severe colitis developing. 1, 2 Monitor stool frequency, physical examination for abdominal tenderness and peritoneal signs, and laboratory tests every 24-48 hours. 2

Do not perform "test of cure" after treatment—clinical improvement is the primary measure of success, not repeat stool testing. 4

Treatment of Recurrent CDI

For first recurrence: Treat based on severity using the same algorithm as initial episode (vancomycin or fidaxomicin). 2, 4

For second and subsequent recurrences: 2, 4

• Vancomycin 125 mg four times daily for at least 10 days followed by tapered or pulsed regimen (e.g., decreasing daily dose by 125 mg every 3 days, or 125 mg every 3 days for 3 weeks)
• Consider fecal microbiota transplantation after multiple recurrences failing appropriate antibiotic treatment 1, 2

Adjunctive Therapy for High-Risk Patients

Bezlotoxumab (monoclonal antibody against toxin B) can be administered to prevent recurrences, particularly in patients with CDI due to the 027 epidemic strain, immunocompromised patients, and those with severe CDI. 4

Common Pitfalls to Avoid

• Never use parenteral vancomycin for CDI—it is not excreted into the colon and is completely ineffective. 4
• Do not delay surgery in fulminant cases waiting for antibiotic response—early colectomy improves outcomes when serum lactate exceeds 5.0 mmol/L or clinical deterioration occurs despite appropriate therapy. 1, 2, 4
• Avoid using metronidazole for severe CDI or for repeated courses due to inferior efficacy and neurotoxicity risk. 1, 3, 4
• Do not use flexible sigmoidoscopy routinely—reserve it for cases with high clinical suspicion but negative stool tests, as colonoscopy carries increased perforation risk in fulminant colitis. 1

Infection Control

Place patients in private rooms with dedicated toilet facilities when possible, use contact precautions with gown and gloves, and perform hand hygiene with soap and water (not alcohol-based sanitizers, which do not kill C. difficile spores). 1, 4 Environmental cleaning with sporicidal disinfectants is essential. 4