What is the best treatment approach for a 72-year-old patient with severe C. diff infection, presenting with fever, hypotension, and leukocytosis, who has previously been treated with vancomycin?

Treatment of Fulminant C. difficile Infection in an Elderly Patient with Prior Vancomycin Treatment

For a 72-year-old patient with fulminant C. difficile infection presenting with fever, hypotension, and severe leukocytosis (WBC 22,000) who has previously been treated with vancomycin, high-dose oral vancomycin (500 mg four times daily) plus intravenous metronidazole (500 mg every 8 hours) is the recommended treatment regimen.

Clinical Assessment and Classification

This patient's presentation meets the criteria for fulminant C. difficile infection based on:

• Age >65 years (72 years old)
• Fever
• Hypotension
• Severe leukocytosis (WBC 22,000/mm³)
• Previous treatment with vancomycin (suggesting possible treatment failure or recurrence)

According to the IDSA/SHEA guidelines, fulminant CDI is defined by the presence of hypotension, shock, ileus, or megacolon 1.

Treatment Recommendations

First-line Treatment:

1. Oral vancomycin 500 mg four times daily

   • Higher dose than standard therapy is required for fulminant disease
   • Strong recommendation, moderate quality of evidence 1

2. Intravenous metronidazole 500 mg every 8 hours concurrently

   • Should be administered together with oral vancomycin
   • Particularly important if ileus is present
   • Strong recommendation, moderate quality of evidence 1

3. If ileus is present: Add rectal vancomycin 500 mg in approximately 100 mL normal saline every 6 hours as a retention enema

   • Weak recommendation, low quality of evidence 1

Duration of Therapy:

• Standard course is 10-14 days
• Consider extending treatment duration in patients with delayed response 1

Special Considerations

Monitoring:

• Closely monitor vital signs, particularly blood pressure
• Follow WBC count to assess response to therapy
• Monitor renal function, especially in patients >65 years of age 2
• Assess for resolution of diarrhea and abdominal pain

Supportive Care:

• Fluid resuscitation for hypotension
• Electrolyte replacement as needed
• Consider ICU admission for hemodynamic monitoring if severely hypotensive

Surgical Consultation:

• Early surgical consultation is recommended for patients with fulminant CDI 1
• Consider surgical intervention for patients who deteriorate or fail to improve within 24-48 hours

Rationale for Treatment Choice

The recommendation for high-dose oral vancomycin plus IV metronidazole is based on:

1. IDSA/SHEA guidelines specifically recommend this combination for fulminant CDI 1
2. Studies have shown protection from complications with initial use of vancomycin (OR 0.24) 3
3. The FDA label for oral vancomycin supports its use in severe and fulminant cases 2
4. The patient's previous treatment with vancomycin suggests possible treatment failure or recurrence, necessitating a more aggressive approach

Common Pitfalls to Avoid

• Inadequate dosing: Using standard dose (125 mg) vancomycin for fulminant disease instead of the recommended 500 mg four times daily
• Monotherapy: Using only vancomycin or only metronidazole instead of combination therapy for fulminant disease
• Delayed surgical consultation: Failing to involve surgical team early in the management of fulminant CDI
• Continuing inciting antibiotics: Ongoing use of exacerbating antibiotics is associated with increased risk of complications (OR 3.02) 3
• Inadequate monitoring: Failing to closely monitor elderly patients for nephrotoxicity during and after vancomycin treatment 2

Alternative Considerations

If the patient fails to respond to the recommended regimen:

• Consider fecal microbiota transplantation (FMT) for multiple recurrences 1
• Fidaxomicin 200 mg twice daily could be considered for recurrent episodes, though data in fulminant disease are limited 1

This aggressive treatment approach is essential given the patient's age, severity of presentation, and previous treatment with vancomycin, all of which place them at high risk for complications and mortality from C. difficile infection.