What is the diagnosis and treatment approach for a patient suspected of having Clostridioides (C. difficile) infection?

Diagnosis and Treatment of Clostridioides difficile Infection

The diagnosis of Clostridioides difficile infection (CDI) requires both clinical symptoms (≥3 unformed stools in 24 hours) and a positive laboratory test, with treatment determined by disease severity and recurrence risk.1

Diagnosis

Clinical Presentation

• CDI presents with diarrhea (≥3 unformed stools in 24 hours), abdominal pain, cramps, bloating, and in severe cases, ileus or toxic megacolon 1, 2
• Risk factors include recent antibiotic therapy, hospitalization, advanced age, comorbidities, and proton pump inhibitor use 1, 2
• Laboratory tests cannot distinguish between colonization and infection, so testing should only be performed on symptomatic patients 2

Diagnostic Testing

• Nucleic acid amplification tests (NAATs) for C. difficile toxin genes are highly sensitive and specific and can be used as a standard diagnostic test 2
• A two-step algorithm is recommended for optimal diagnosis 1:
  • First step: Screening with glutamate dehydrogenase (GDH) test (high sensitivity) 2
  • Second step: Confirmation with toxin A/B enzyme immunoassay (EIA) testing (high specificity) 2
• Single-step PCR on liquid stool samples also provides high sensitivity and specificity 2
• "Test of cure" is not recommended after CDI treatment 2
• Repeat testing during the same diarrheal episode is only useful in selected cases with ongoing clinical suspicion 2

Additional Diagnostic Methods

• Flexible sigmoidoscopy may be helpful when there is high clinical suspicion but negative stool tests 2
• Imaging (CT scan, ultrasound) can help diagnose severe complications such as toxic megacolon or perforation 2

Treatment

General Principles

• Treatment should be based on disease severity and recurrence risk 2
• Discontinue the inciting antibiotic if possible 2
• Avoid antiperistaltic agents and opiates 2
• Empirical therapy should be avoided unless there is strong suspicion for severe CDI 2

Initial Episode Treatment

• Mild-moderate CDI:

  • Metronidazole 500 mg orally three times daily for 10 days 2, 1
  • Note: Repeated or prolonged courses of metronidazole should be avoided due to risk of cumulative and potentially irreversible neurotoxicity 2

• Severe CDI:

  • Vancomycin 125 mg orally four times daily for 10 days 2
  • Severity markers include: leukocytosis >15,000/μL, serum creatinine rise >50% above baseline, albumin <3 g/dL, or pseudomembranous colitis 2

• Severe complicated CDI (hypotension, shock, ileus, megacolon):

  • Vancomycin 125-500 mg orally four times daily 2
  • If oral therapy impossible: Metronidazole 500 mg IV every 8 hours AND vancomycin 500 mg via nasogastric tube or as retention enema 2
  • Consider surgical consultation for colectomy if perforation or deteriorating condition despite antibiotics 2

Recurrent CDI Treatment

• First recurrence:

  • Repeat initial therapy based on severity 2
  • Consider fidaxomicin 200 mg orally twice daily for 10 days if high risk of further recurrence 3, 2

• Second or later recurrences:

  • Vancomycin oral taper/pulse 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 2
  • Consider fidaxomicin 200 mg twice daily for 10 days 3, 2
  • Consider fecal microbiota transplantation (FMT), which has shown high success rates for multiple recurrences 2, 4

Emerging Therapies

• Bezlotoxumab (monoclonal antibody against C. difficile toxin B) can be considered for prevention of recurrence in high-risk patients 5, 4
• Fecal microbiota transplantation shows promising results for recurrent CDI with symptom resolution rates of approximately 80-90% 2, 4

Prevention and Infection Control

• Rapid isolation of infected patients is crucial to control transmission 1
• Implement contact precautions with gloves and gowns 1
• Thorough environmental cleaning with sporicidal agents 5
• Antibiotic stewardship to minimize unnecessary antibiotic use 2, 1

Monitoring and Follow-up

• Monitor for clinical response (decreased stool frequency, improved consistency) within 3-5 days of treatment initiation 2
• Watch for complications including dehydration, electrolyte disturbances, and acute kidney injury 1
• Be aware that post-infectious irritable bowel syndrome can occur in approximately 4.3% of patients more than three months after infection 1