What is the treatment for Clostridium difficile (C. diff) diarrhea?

Treatment of Clostridium difficile Diarrhea

Vancomycin 125 mg orally four times daily for 10 days is the first-line treatment for both non-severe and severe C. difficile infection, replacing metronidazole as the preferred initial therapy. 1, 2, 3

Immediate Management Steps

Discontinue Inciting Antibiotics

• Stop the precipitating antibiotic immediately if clinically feasible, as continued use significantly increases recurrence risk and decreases clinical response 1, 3
• If ongoing antibiotic therapy is required for another infection, switch to agents less associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 1, 3

Classify Disease Severity

• Non-severe CDI: Stool frequency <4 times daily, no signs of severe colitis 1, 2
• Severe CDI: Temperature >38.5°C, hemodynamic instability, WBC >15×10⁹/L, creatinine rise >50% above baseline, elevated lactate, pseudomembranous colitis on endoscopy, or colonic wall thickening on imaging 2
• Fulminant CDI: Hypotension, shock, ileus, or megacolon 2

First-Line Antibiotic Treatment

Initial Episode (Non-Severe or Severe)

• Vancomycin 125 mg orally four times daily for 10 days 1, 2, 3, 4
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days, particularly for patients at high risk of recurrence (elderly, multiple comorbidities, concomitant antibiotics) 1, 2, 5
• Metronidazole 500 mg orally three times daily for 10 days should only be used in settings where vancomycin or fidaxomicin access is limited, and only for non-severe disease 1, 3

The 2018 IDSA/SHEA guidelines represent a major shift from older recommendations: two randomized controlled trials demonstrated vancomycin superiority over metronidazole, with cure rates of 97% vs 84% overall (P<0.006) and 97% vs 76% in severe disease (P=0.02) 1. Metronidazole is no longer recommended as first-line therapy due to higher failure rates and risk of cumulative neurotoxicity with repeated courses 1, 2, 3.

Fulminant CDI

• Vancomycin 500 mg orally four times daily PLUS metronidazole 500 mg IV every 8 hours 2
• If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1, 2
• Consider vancomycin 500 mg four times daily via nasogastric tube if oral route compromised 1

Treatment of Recurrent CDI

First Recurrence

• Treat based on severity using the same algorithm as initial episode 2
• Consider fidaxomicin 200 mg twice daily for 10 days or vancomycin in a tapered and pulsed regimen 2, 3

Second and Subsequent Recurrences

• Vancomycin 125 mg orally four times daily for at least 10 days, followed by tapered and pulsed regimen (e.g., decreasing daily dose by 125 mg every 3 days, then 125 mg every 3 days for 3 weeks) 1, 2
• Fecal microbiota transplantation (FMT) is effective for multiple recurrences after failed appropriate antibiotic treatments 1, 2, 3

Approximately 25% of patients experience at least one recurrence, creating a challenging cycle 3. FMT restores intestinal microbiota balance by reintroducing normal flora via donor stool, correcting the dysbiosis that allows C. difficile overgrowth 1.

Surgical Intervention

Colectomy should be performed for:

• Perforation of the colon 1, 2
• Systemic inflammation with deteriorating clinical condition not responding to antibiotics 1, 2
• Toxic megacolon or severe ileus 1, 2
• Perform surgery before serum lactate exceeds 5.0 mmol/L 1, 2

Diverting loop ileostomy with colonic lavage is an alternative to total colectomy 1.

Critical Adjunctive Measures

Infection Control

• Use soap and water for hand hygiene, NOT alcohol-based sanitizers, as alcohol does not kill C. difficile spores or remove them from hands 1, 2, 3
• Implement contact precautions for all healthcare workers 3

Medications to Avoid

• Avoid antiperistaltic agents and opiates as they can precipitate toxic megacolon 1
• Discontinue unnecessary proton pump inhibitors in high-risk patients, though evidence for this is limited 1, 2

Monitoring Treatment Response

• Assess clinical response by 72 hours: stool frequency should decrease or consistency improve 1, 3
• Treatment failure is defined as absence of improvement after 3 days 1, 3
• If no improvement occurs, escalate therapy rather than continuing the same regimen 3

Common Pitfalls

• Do not use metronidazole for severe CDI due to significantly higher failure rates 2
• Avoid repeated or prolonged metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 3
• Do not delay empiric treatment in fulminant CDI or when substantial laboratory delay is expected (>48 hours) 1
• Do not rely on probiotics for prevention, as data are insufficient and formulations may cause infections in hospitalized patients 1