Initial Treatment for Clostridioides difficile Infection in Outpatient Settings

Disease Severity Assessment

The Infectious Diseases Society of America recommends that non-severe CDI be defined by leukocytosis with WBC ≤15,000 cells/mL, serum creatinine <1.5 mg/dL, stool frequency <4 times daily, and no signs of severe colitis 1
Severe CDI is characterized by leukocytosis with WBC ≥15,000 cells/mL, serum creatinine >1.5 mg/dL, fever, rigors, hemodynamic instability, and signs of peritonitis or ileus 1

The American College of Gastroenterology recommends oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days as first-line therapy for initial CDI 1
For fulminant CDI, the Infectious Diseases Society of America recommends oral vancomycin 500 mg four times daily, and if ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1

The Infectious Diseases Society of America recommends discontinuing the inciting antibiotic agent(s) as soon as possible to reduce the risk of CDI recurrence 1
The Society for Healthcare Epidemiology of America recommends starting empiric therapy if substantial delay in laboratory confirmation is expected (>48 hours) or for fulminant CDI 1
The European Society of Clinical Microbiology and Infectious Diseases recommends avoiding antimotility agents such as loperamide and opiates, especially in the acute setting, as they may worsen outcomes 2

Fidaxomicin shows similar efficacy to vancomycin for initial cure, and may be particularly useful for patients at high risk for recurrence, according to the World Journal of Emergency Surgery 3

The Infectious Diseases Society of America recommends assessing disease severity before selecting treatment to avoid failure 1
The Society for Healthcare Epidemiology of America recommends discontinuing the inciting antibiotic when it could be discontinued to reduce the risk of CDI recurrence 1

Oral metronidazole 500 mg three times daily for 10 days may be considered in settings where access to vancomycin or fidaxomicin is limited, but it should be limited to initial episodes of mild-moderate CDI due to increasing treatment failures 4
The American Medical Association recommends vancomycin over metronidazole for mild-moderate CDI due to lower clinical success rates for metronidazole 5, 6

Factors associated with metronidazole failures include age > 60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, and abnormal abdominal CT imaging 6
Patients receiving metronidazole have a longer time to symptomatic improvement than patients receiving vancomycin 6

For first recurrence of mild-moderate CDI, oral metronidazole or vancomycin is recommended 7
For subsequent recurrences, vancomycin is the recommended therapy, often with pulsed or tapering courses 7

Repeated or prolonged courses of metronidazole should be avoided due to risk of cumulative and potentially irreversible neurotoxicity 4