What is the treatment for outpatient Clostridioides difficile (C. diff) infection?

Outpatient Treatment of Clostridioides difficile Infection

For initial outpatient C. difficile infection, treat with oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days as first-line therapy. 1, 2, 3

Disease Severity Assessment Before Treatment

Before selecting therapy, assess disease severity to guide appropriate treatment selection:

Non-severe CDI is characterized by:

• Stool frequency < 4 times daily 1, 2
• White blood cell count < 15 × 10⁹/L 1, 2
• Serum creatinine < 1.5 mg/dL 3
• No signs of severe colitis 1, 2

Severe CDI is defined by one or more of:

• White blood cell count ≥ 15 × 10⁹/L 2, 3
• Serum creatinine > 1.5 mg/dL 3
• Fever > 38.5°C 2
• Hemodynamic instability 2, 3
• Signs of peritonitis or ileus 2, 3

First-Line Treatment Options

For non-severe CDI:

• Oral vancomycin 125 mg four times daily for 10 days 2, 3
• OR oral fidaxomicin 200 mg twice daily for 10 days 2, 3, 4
• Metronidazole 500 mg three times daily for 10 days may be considered only in settings where access to vancomycin or fidaxomicin is limited, but should be avoided due to increasing treatment failures 1, 3

For severe CDI:

• Oral vancomycin 125 mg four times daily for 10 days is the recommended first-line treatment 2
• Fidaxomicin 200 mg twice daily for 10 days is an alternative and may be preferred due to lower rates of secondary recurrences 1, 4

Important Caveat About Metronidazole

While older guidelines recommended metronidazole for non-severe disease, current recommendations strongly favor vancomycin or fidaxomicin over metronidazole due to lower clinical success rates with metronidazole 3. Factors associated with metronidazole failure include age > 60 years, fever, hypoalbuminemia, peripheral leukocytosis, and abnormal abdominal CT imaging 3. Additionally, repeated or prolonged courses of metronidazole carry risk of cumulative and potentially irreversible neurotoxicity 3.

Treatment of Recurrent CDI

For first recurrence:

• Treat based on disease severity, with consideration of vancomycin or fidaxomicin instead of metronidazole even for non-severe cases 2

For second and subsequent recurrences:

• Oral vancomycin 125 mg four times daily for at least 10 days with consideration of vancomycin taper/pulse strategy 2
• OR fidaxomicin 200 mg twice daily for 10 days (associated with lower recurrence rates) 1, 2, 4
• OR oral vancomycin followed by rifaximin 1

For multiple recurrent CDI (≥2 recurrences):

• Fecal microbiota transplantation (FMT) should be offered to patients who have had at least two recurrences, or those who have had one recurrence and have risk factors for further episodes 5, 1
• FMT prevention of CDI recurrence ranges from 70% to 90% 1
• FMT should be given upon completion of a course of standard antibiotics, with antibiotics ideally stopped 1-3 days before conventional FMT 1

Essential Adjunctive Measures

Discontinue the inciting antibiotic as soon as clinically possible to reduce risk of CDI recurrence 1, 2, 3

Avoid antiperistaltic agents and opiates, especially in the acute setting, as they may worsen outcomes 1, 2, 3

Monitoring Treatment Response

• Monitor for clinical response within 3 days of treatment initiation 2
• Treatment failure is defined as absence of improvement after 3-5 days 2
• Clinical response should be the primary measure of treatment success rather than repeat stool testing 1

Common Pitfalls to Avoid

• Do not use metronidazole as first-line therapy when vancomycin or fidaxomicin are available 3
• Do not skip doses or stop treatment early, even if symptoms improve, as this increases risk of recurrence and antibiotic resistance 4
• Do not delay FMT consideration in patients with multiple recurrences—offer after second recurrence or earlier if risk factors present 5
• Do not use antiperistaltic agents or opiates during acute infection 1, 2, 3