What is the treatment for Clostridioides difficile (C. diff) infection in a patient who is unable to take oral (PO) medications?

Treatment for C. difficile Infection in Patients Unable to Take Oral Medications

For patients with C. difficile infection who cannot take oral medications, the recommended treatment is intravenous metronidazole 500 mg three times daily for 10 days, plus either intracolonic vancomycin 500 mg in 100 mL of normal saline every 4-12 hours via retention enema or vancomycin 500 mg four times daily via nasogastric tube. 1

Treatment Algorithm Based on Disease Severity

Non-severe C. difficile infection:

• Intravenous metronidazole 500 mg three times daily for 10 days 1

Severe C. difficile infection:

• Intravenous metronidazole 500 mg three times daily for 10 days 1
• PLUS one or both of the following:
  • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours via retention enema 1
  • Vancomycin 500 mg four times daily via nasogastric tube 1

Defining Severe C. difficile Infection

Severe infection is characterized by one or more of the following:

• Fever (core body temperature > 38.5°C) 1
• Hemodynamic instability or signs of septic shock 1
• Signs of peritonitis 1
• Signs of ileus (vomiting, absent passage of stool) 1
• Marked leukocytosis (WBC > 15 × 10^9/L) 1
• Serum creatinine rise (>50% above baseline) 1
• Elevated serum lactate 1
• Radiological evidence of colonic distension, wall thickening, or pericolonic fat stranding 1

Treatment for Recurrent C. difficile Infection

For patients with recurrent C. difficile infection who cannot take oral medications:

• Metronidazole 500 mg three times daily intravenously for 10-14 days 1
• PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 1
• AND/OR vancomycin 500 mg four times daily via nasogastric tube 1

Special Considerations

Surgical Intervention

Consider colectomy in patients with:

• Perforation of the colon 1
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy 1
• Toxic megacolon or severe ileus 1
• Serum lactate > 5.0 mmol/L (surgery should be performed before lactate reaches this level) 1

Alternative Approaches

• In patients with stomas or colon diversions, trans-stoma vancomycin may be effective 1
• For patients with multiple recurrences who have failed appropriate antibiotic therapy, fecal microbiota transplantation should be considered once oral intake is possible 1

Important Caveats

• Metronidazole is no longer recommended as first-line therapy for adults who can take oral medications, but remains the backbone of parenteral therapy 2
• Fidaxomicin is a newer option for oral therapy but has no established parenteral formulation 1
• Antiperistaltic agents and opiates should be avoided as they may worsen C. difficile infection 1
• Discontinue the inciting antibiotic if possible, or switch to antibiotics less frequently associated with C. difficile infection 1
• Treatment response should be assessed by decreased stool frequency and improved consistency within 3 days, with no new signs of severe colitis 1