What is the recommended management for a patient with a suspected or confirmed Clostridioides difficile (C diff) infection, considering their medical history and potential complications?

Management of Clostridioides difficile Infection

Fidaxomicin 200 mg orally twice daily for 10 days is the preferred first-line treatment for initial C. difficile infection in adults and children ≥6 months, with oral vancomycin 125 mg four times daily for 10 days as an acceptable alternative. 1

Initial Assessment and Diagnosis

Diagnostic Criteria

• Only test symptomatic patients with diarrhea (≥3 unformed stools in 24 hours) AND a positive stool test for toxigenic C. difficile or colonoscopic evidence of pseudomembranous colitis 1
• Never perform "test of cure" after treatment completion, as this is not recommended 1
• Use multistep PCR approaches or single-step PCR on liquid stool for highest sensitivity and specificity 1

Severity Classification

Assess disease severity immediately to guide treatment intensity:

Non-severe CDI: 2, 3

• Stool frequency <4 times daily
• WBC ≤15,000 cells/μL
• Serum creatinine <1.5 mg/dL

Severe CDI: 3

• WBC ≥15,000 cells/μL
• Serum creatinine >1.5 mg/dL
• Fever present
• Signs of severe colitis

Fulminant CDI: 2, 3

• Hypotension or shock
• Ileus or toxic megacolon
• Colonic perforation
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Colonic wall thickening or pericolonic fat stranding on imaging

Treatment by Severity

Initial Episode - Non-Severe Disease

First-line options: 1

• Fidaxomicin 200 mg orally twice daily for 10 days (preferred)
• Vancomycin 125 mg orally four times daily for 10 days (acceptable alternative)

Last resort only (when preferred agents unavailable): 1

• Metronidazole 500 mg orally three times daily for 10-14 days
• Use ONLY if WBC ≤15,000 cells/μL AND creatinine <1.5 mg/dL

Initial Episode - Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days 1, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is also appropriate 3

Fulminant Disease

Combination therapy required: 1, 3

• Vancomycin 500 mg orally or by nasogastric tube four times daily
• PLUS intravenous metronidazole 500 mg every 8 hours
• If oral route impossible, add intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 2

Surgical Intervention

Perform colectomy urgently for: 2

• Colonic perforation
• Toxic megacolon or severe ileus not responding to antibiotics
• Systemic inflammation with clinical deterioration
• Operate before serum lactate exceeds 5.0 mmol/L (critical threshold)

Recurrent CDI Management

First Recurrence

Preferred options: 1

• Fidaxomicin 200 mg twice daily for 10 days (especially if vancomycin used initially)
• Vancomycin 125 mg four times daily for 10 days (especially if metronidazole used initially)

Consider bezlotoxumab adjunctive therapy (10 mg/kg IV once during antibiotic treatment) for high-risk patients: 1

• Age >65 years
• Immunocompromised status
• Severe initial CDI
• Concomitant antibiotic use required

Second and Subsequent Recurrences

• Vancomycin 125 mg four times daily for at least 10 days 2
• Consider taper/pulse strategy: decrease daily dose by 125 mg every 3 days, then pulse dosing of 125 mg every 3 days for 3 weeks 2
• Fidaxomicin extended regimen is also appropriate 1, 3

Critical Supportive Measures

Antibiotic Management

Immediately discontinue the inciting antibiotic if possible 1, 3

If continued antibiotics necessary, switch to lower-risk agents: 1

• Parenteral aminoglycosides
• Sulfonamides
• Macrolides
• Vancomycin
• Tetracycline/tigecycline

Avoid high-risk antibiotics: 1

• Clindamycin
• Third-generation cephalosporins
• Penicillins
• Fluoroquinolones

Additional Measures

• Avoid antiperistaltic agents and opiates 2, 3
• Consider discontinuing proton pump inhibitors if not essential 3
• Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores) 4

Monitoring Treatment Response

Expected Timeline

• Clinical improvement should occur within 3-5 days of starting therapy 1, 3
• Look for decreased stool frequency and improved stool consistency after 3 days 2, 3

Treatment Failure Definition

• Absence of response after 3-5 days 1, 3
• New signs of severe colitis develop 2

Recurrence Definition

• Return of symptoms with microbiological evidence of toxin-producing C. difficile after initial response 2, 1
• Increased stool frequency for two consecutive days with looser stools 2

Pediatric Considerations

Dosing (≥6 months to <18 years)

Tablets (for patients ≥12.5 kg who can swallow tablets): 5

• Fidaxomicin 200 mg orally twice daily for 10 days

Oral suspension (weight-based): 5

• 4 kg to <7 kg: 80 mg (2 mL) twice daily
• 7 kg to <9 kg: 120 mg (3 mL) twice daily
• 9 kg to <12.5 kg: 160 mg (4 mL) twice daily
• ≥12.5 kg: 200 mg (5 mL) twice daily

Special Testing Considerations

• Do not test children <12 months due to high rates of asymptomatic colonization 4
• Children 1-2 years: test only after excluding other causes of diarrhea 4

Common Pitfalls to Avoid

• Never use metronidazole as first-line when fidaxomicin or vancomycin are available due to concerns about resistance 1, 6
• Never test asymptomatic patients regardless of exposure history 1, 4
• Never perform test of cure after treatment completion 1
• Do not delay surgical consultation in fulminant disease—operate before lactate exceeds 5.0 mmol/L 2
• Remember that alcohol-based hand sanitizers are ineffective against C. difficile spores 4