What are the diagnostic steps and treatment options for Clostridioides difficile (C. diff) infection in a patient presenting with diarrhea?

Diagnosis of C. difficile Infection in Patients with Diarrhea

Testing for C. difficile should be performed in patients >2 years of age who have diarrhea and risk factors such as recent antimicrobial use, healthcare-associated diarrhea, or persistent unexplained diarrhea. 1, 2

Diagnostic Approach

When to Test for C. difficile

• Test patients with diarrhea who have:
  • History of antimicrobial use within previous 8-12 weeks
  • Healthcare-associated diarrhea
  • Persistent diarrhea without another identified cause
  • Age >2 years (high rates of asymptomatic colonization make testing in infants unreliable) 1

Optimal Specimen Collection

1. Preferred specimen: Fresh diarrheal stool sample (takes shape of container) 1
2. Alternative: Perirectal swab if stool cannot be obtained (95.7% sensitivity, 100% specificity) 2
3. Timing: Collect a single diarrheal stool specimen - multiple specimens do not increase yield 1

Recommended Testing Methods

The Infectious Diseases Society of America recommends one of these approaches 1, 2:

1. Two-step algorithm (preferred):

   • GDH (glutamate dehydrogenase) screening + toxin A/B testing
   • OR
   • NAAT (nucleic acid amplification test) + toxin confirmation

2. Single-step testing:

   • NAAT for toxigenic C. difficile
   • Toxin detection by enzyme immunoassay (EIA)

Important Diagnostic Considerations

• Testing should not be performed on formed stool (asymptomatic carriers)
• Do not perform "test of cure" after treatment completion 2, 3
• Testing in children <2 years should be avoided due to high rates of asymptomatic colonization (up to 70%) 1
• Toxin A-negative, B-positive strains can cause severe disease and would be missed by toxin A-only tests 4

Clinical Assessment

Symptoms to Evaluate

• Watery diarrhea (most common)
• Abdominal pain or cramping
• Fever
• Leukocytosis
• Hypoalbuminemia in severe cases 2

Disease Classification

Classify severity to guide treatment 2:

• Non-severe: Diarrhea without significant systemic symptoms
• Severe: Leukocytosis ≥15,000 cells/μL or serum creatinine ≥1.5 mg/dL
• Fulminant: Hypotension, shock, ileus, or megacolon

Differential Diagnosis

Consider other causes of infectious diarrhea, particularly in community-acquired cases:

• Viral gastroenteritis (most common cause of acute diarrhea) 5
• Bacterial pathogens: Salmonella, Shigella, Campylobacter, Yersinia 1
• Parasitic infections
• Inflammatory bowel disease

Common Pitfalls to Avoid

1. Testing asymptomatic patients (leads to unnecessary treatment)
2. Testing children <2 years without strong clinical suspicion
3. Using toxin A-only tests (will miss toxin A-negative, B-positive strains)
4. Failing to consider C. difficile in outpatients with diarrhea after antibiotic exposure
5. Performing multiple tests on the same specimen (does not increase yield) 1

Once C. difficile infection is confirmed, prompt treatment with oral vancomycin, fidaxomicin, or metronidazole (for non-severe cases only) should be initiated based on disease severity, with infection control measures implemented to prevent transmission 2, 6.