What are the latest guidelines for diagnosing and managing Clostridioides difficile (C. diff) diarrhea?

Diagnosis and Management of Clostridioides difficile Infection: Evidence-Based Guidelines

Diagnostic Approach

Test only symptomatic patients with clinically significant diarrhea (≥3 unformed stools in 24 hours) who have risk factors such as recent antibiotic use, healthcare exposure, or advanced age. 1, 2

When to Test

• Test patients >2 years of age with diarrhea following antimicrobial use within the preceding 8-12 weeks 1
• Test healthcare-associated diarrhea occurring >72 hours after hospital admission 1
• Consider testing in persistent diarrhea without identified etiology, even without classic risk factors 1
• Do NOT test asymptomatic patients or those with formed stools—this detects colonization, not infection 1, 2
• Do NOT test children <2 years old routinely due to high rates (up to 70%) of asymptomatic colonization 1

Optimal Diagnostic Algorithm

Use a two-step algorithm for maximum accuracy: 1, 2

1. First step (screening): Nucleic acid amplification test (NAAT/PCR) OR glutamate dehydrogenase (GDH) antigen detection (high sensitivity: 0.91-1.00) 1, 2

2. Second step (confirmation): If screening positive, perform toxin detection (higher specificity: 0.98) 1, 2

This two-step approach achieves sensitivity of 0.91 and specificity of 0.98, avoiding both false positives from colonization and false negatives from low toxin levels 2.

Specimen Collection

• Submit a single diarrheal stool specimen (one that takes the shape of the container)—multiple specimens do not increase yield 1
• Fresh stool is preferred for optimal toxin detection 1
• For patients with ileus who cannot produce stool, PCR testing of perirectal swabs is acceptable 1

Common Diagnostic Pitfalls

• Avoid relying solely on toxin EIA testing—it has suboptimal sensitivity (0.70-0.80) and misses many cases 2
• Do NOT order "test of cure" after treatment—patients shed spores for up to 6 weeks post-treatment 2
• Do NOT submit multiple specimens—this increases false positives without improving detection 1

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Treatment Algorithm

Initial Episode: Mild-to-Moderate CDI

For mild-to-moderate disease (no severe systemic symptoms), oral vancomycin 125 mg four times daily for 10 days is now preferred over metronidazole. 2, 3

• Metronidazole 500 mg three times daily for 10 days can be used if vancomycin is unavailable, but is considered inferior 1, 4
• Clinical success rates with vancomycin are approximately 81% 1, 2

Initial Episode: Severe CDI

For severe CDI (defined as WBC >15,000 cells/mm³, serum creatinine >1.5 mg/dL, pseudomembranous colitis, ICU admission, or age ≥60 with fever >38.3°C and albumin <2.5 mg/dL), use oral vancomycin 125 mg four times daily for 10 days. 1, 3

Recurrent CDI

For first recurrence, use fidaxomicin 200 mg orally twice daily for 10 days—this reduces subsequent recurrence risk compared to vancomycin. 2, 5, 6

• Fidaxomicin is a microbiome-sparing antibiotic with clinical success rates of approximately 81% and lower recurrence rates 2, 6
• For pediatric patients ≥6 months: Fidaxomicin is FDA-approved with weight-based dosing (see FDA label for specific dosing) 5

Multiple Recurrences (≥2 recurrences)

For multiple recurrences, fecal microbiota transplantation (FMT) achieves approximately 90% success rates and is the treatment of choice. 2, 4

• Defined microbiome biotherapeutics offer a safer, more controlled alternative to traditional FMT 6

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Critical Management Principles

Antibiotic Stewardship

• Discontinue non-CDI antibiotics if clinically feasible—this is essential for treatment success 1, 2
• Avoid empirical therapy except in cases of strong clinical suspicion of severe CDI where diagnostic delay would be harmful 1

Infection Control Measures

Implement contact precautions immediately upon diagnosis: 1

• Use gloves and gowns for all patient contact 1
• Perform daily environmental sporicidal disinfection (bleach-based products) 1
• Isolate infected patients rapidly to prevent transmission 1, 2
• Educate healthcare workers on prevention strategies 1

Monitoring for Complications

Watch for severe complications including: 1, 2

• Dehydration and electrolyte disturbances
• Acute kidney injury
• Toxic megacolon
• Bowel perforation
• Post-infectious irritable bowel syndrome (occurs in ~4.3% of patients >3 months post-infection) 2

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Special Populations

Inflammatory Bowel Disease (IBD)

• Test all IBD patients with diarrhea flares for C. difficile, as clinical presentation overlaps with IBD exacerbation 1, 7

Long-Term Care Facilities

• Suspect CDI in any resident exposed to antibiotics in the previous 30 days who develops ≥3 watery stools in 24 hours or abdominal pain 7, 3

Pediatric Considerations

• Children ≥6 months can receive fidaxomicin using weight-based dosing (tablets for ≥12.5 kg, oral suspension for 4-12.5 kg) 5
• Avoid testing children <2 years due to high colonization rates 1