What is the recommended treatment for a patient with Clostridioides (C.) difficile colitis?

Treatment of Clostridioides difficile Colitis

For initial nonsevere C. difficile infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the preferred first-line treatments, with metronidazole no longer recommended. 1

Initial Episode: Nonsevere Disease

Disease Severity Classification:

• Nonsevere disease is defined by white blood cell count ≤15,000 cells/μL AND serum creatinine <1.5 mg/dL 1

First-Line Antibiotic Options:

• Oral vancomycin 125 mg four times daily for 10 days is the preferred treatment, demonstrating superior clinical outcomes compared to metronidazole 1, 2
• Fidaxomicin 200 mg twice daily for 10 days is equally acceptable as first-line therapy, particularly for patients at high risk for recurrence (elderly, multiple comorbidities) 1, 3
• Metronidazole is no longer recommended as first-line therapy due to inferior sustained response rates 4, 5

Initial Episode: Severe Disease

Disease Severity Classification:

• Severe disease is characterized by white blood cell count >15,000 cells/μL OR serum creatinine ≥1.5 mg/dL 1

Treatment Approach:

• Oral vancomycin 125 mg four times daily for 10 days remains the standard approach, with high-quality evidence demonstrating superiority over metronidazole in severe disease 1

Initial Episode: Fulminant Disease

Disease Severity Classification:

• Fulminant disease includes hypotension/shock, ileus, or megacolon 1

Aggressive Medical Management:

• Oral vancomycin 500 mg four times daily (higher dose) by mouth or nasogastric tube 1
• Add intravenous metronidazole 500 mg every 8 hours in conjunction with oral vancomycin, particularly if ileus is present 1
• Consider rectal vancomycin instillation (500 mg in 100 mL normal saline every 4-12 hours) if ileus prevents oral administration 1
• Early surgical consultation is critical; colectomy should be performed before severe deterioration, ideally before serum lactate exceeds 5.0 mmol/L 1

Surgical Options:

• Loop ileostomy with antegrade vancomycin flushes via ileostomy (continued every 6 hours for 10 days) resulted in reduced mortality compared to historical controls, with colon preservation achieved in 93% of patients 4
• Adjusted mortality was significantly lower in the loop ileostomy group compared to total colectomy (17.2% vs. 39.7%; p = 0.002) 4

Essential Supportive Care Measures

Immediate Interventions:

• Discontinue the inciting antibiotic immediately if clinically possible, as this is critical for treatment success 1
• Switch to lower-risk antibiotics if continued antimicrobial therapy is necessary: parenteral aminoglycosides, sulfonamides, macrolides, or tetracyclines are preferred 1
• Avoid high-risk antibiotics: clindamycin, third-generation cephalosporins, fluoroquinolones, and penicillins are strongly associated with CDI 1

Additional Supportive Measures:

• Intravenous fluid resuscitation, albumin supplementation (particularly if serum albumin <2 g/dL), and electrolyte replacement should be provided to all patients with severe C. difficile infection 4
• Discontinue proton pump inhibitors if not absolutely required, as they increase CDI risk and recurrence 1
• Avoid antiperistaltic agents and opiates, which can worsen disease 1
• Early detection of shock and aggressive management of underlying organ dysfunction are essential for improved outcomes in fulminant colitis 4

First Recurrence

Preferred Treatment Options:

• Fidaxomicin 200 mg twice daily for 10 days demonstrates lower recurrence rates compared to vancomycin 1
• Extended fidaxomicin regimen (200 mg twice daily for 5 days, then once every other day for 20 days) may be considered 1
• Tapered and pulsed vancomycin regimen: 125 mg four times daily for 10-14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2-3 days for 2-8 weeks 1
• Vancomycin (particularly if metronidazole was used for the first episode) or fidaxomicin are the agents of choice for first recurrence 4

Multiple Recurrences (Second or Subsequent)

Definitive Treatment:

• Fecal microbiota transplantation (FMT) is strongly recommended after failure of appropriate antibiotic treatments for at least 2 recurrences (3 total CDI episodes), with 87-92% clinical resolution rates 1
• Antibiotic treatment options for patients with >1 recurrence include oral vancomycin therapy using a tapered and pulsed regimen 4

Critical Pitfalls to Avoid

Common Errors:

• Never use intravenous vancomycin for CDI treatment, as it is not excreted into the colon and has no effect on CDI 2
• Oral vancomycin must be given orally for treatment; parenteral administration is not effective 2
• Metronidazole should not be used for long-term therapy because of the potential for cumulative neurotoxicity 4
• Consider treatment extension to 14 days if delayed response occurs 1

Monitoring Requirements:

• Clinically significant serum concentrations of vancomycin have been reported in patients with inflammatory disorders of the intestinal mucosa; monitoring of serum concentrations may be appropriate in patients with renal insufficiency and/or colitis 2
• In patients >65 years of age, renal function should be monitored during and following treatment to detect potential vancomycin-induced nephrotoxicity 2