What is the recommended antibiotic treatment for moderate Clostridioides (C.) difficile infection?

Antibiotic Treatment for Moderate C. difficile Infection

For moderate (non-severe) C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days as first-line therapy. 1, 2

Defining Moderate (Non-Severe) CDI

Moderate CDI is characterized by: 2

• Leukocytosis with WBC ≤15,000 cells/mL
• Serum creatinine <1.5 mg/dL
• Stool frequency <4 times daily
• No signs of severe colitis

First-Line Treatment Options

Preferred Regimens

Oral vancomycin 125 mg four times daily for 10 days 1, 3

• This is the standard dose; higher doses (500 mg four times daily) show no additional benefit for non-severe disease 1
• Vancomycin achieves high fecal concentrations even at low doses 1
• Must be given orally; parenteral vancomycin is NOT effective for CDI 3

Oral fidaxomicin 200 mg twice daily for 10 days 1, 4

• Non-inferior to vancomycin for initial cure 1, 4
• Lower recurrence rates compared to vancomycin (particularly valuable for patients at high risk of recurrence) 1, 2
• More expensive but microbiome-sparing 5

Alternative (When Access Limited)

Oral metronidazole 500 mg three times daily for 10 days 1, 2

• Should only be used when vancomycin or fidaxomicin are unavailable 2
• Inferior clinical success rates compared to vancomycin 2
• Factors predicting metronidazole failure include: age >60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, and abnormal abdominal CT 2
• Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 2

Critical Management Steps

Discontinue Inciting Antibiotics

• Stop the causative antibiotic as soon as possible 2
• This is essential to reduce recurrence risk 2
• If continued antibiotic therapy is required, use agents less frequently implicated in CDI 6

Discontinue Unnecessary PPIs

• Stop proton pump inhibitors if no clear indication exists 6
• PPIs are epidemiologically associated with increased CDI risk 6
• This is part of good antimicrobial stewardship 6

Avoid Antimotility Agents

• Do not use loperamide or opiates, especially in acute settings 2
• These agents may worsen outcomes 2

Treatment Duration Considerations

• Standard treatment course is 10 days 1, 3
• Some patients (particularly those treated with metronidazole) may have delayed response 1
• Consider extending treatment to 14 days if delayed response occurs 1

Common Pitfalls to Avoid

Do not use metronidazole as first-line therapy when vancomycin or fidaxomicin are available 2 - The 2018 IDSA/SHEA guidelines represent a significant shift from older recommendations that favored metronidazole for mild-moderate disease 1

Do not use parenteral vancomycin for CDI treatment 3 - Only oral vancomycin is effective; IV vancomycin does not reach therapeutic concentrations in the colon 3

Monitor for nephrotoxicity in patients >65 years 3 - Oral vancomycin can cause nephrotoxicity, particularly in elderly patients 3

• Monitor renal function during and after treatment in this population 3

Assess for systemic absorption in patients with severe colitis 3 - Patients with inflammatory intestinal mucosa may have significant systemic vancomycin absorption 3

• Consider monitoring serum vancomycin levels in patients with renal insufficiency or severe colitis 3