Treatment of Clostridioides difficile Infection (CDI)

Initial CDI Episode Treatment

The Infectious Diseases Society of America recommends oral vancomycin or fidaxomicin as first-line therapy for CDI, with treatment selection based on disease severity, defined as WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL for non-severe CDI 1, 2
For non-severe CDI, first-line treatment options include vancomycin 125 mg orally 4 times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days, with vancomycin being an alternative if access to fidaxomicin is limited 1, 2
For severe CDI, defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL, first-line treatment options include vancomycin 125 mg orally 4 times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days 1, 3
Higher doses of vancomycin (500 mg four times daily) have not shown significant differences in clinical outcomes compared to standard doses for severe CDI 3

For first recurrence of CDI, treatment options include vancomycin 125 mg orally 4 times daily for 10 days or a prolonged tapered and pulsed vancomycin regimen, with fidaxomicin 200 mg twice daily for 10 days being an alternative if vancomycin was used initially 1
For second or subsequent recurrence of CDI, treatment options include vancomycin in a tapered and pulsed regimen, vancomycin 125 mg 4 times daily for 10 days followed by rifaximin 400 mg 3 times daily for 20 days, or fidaxomicin 200 mg twice daily for 10 days, with fecal microbiota transplantation being particularly effective for multiple recurrences 1, 5

For NPO patients, treatment options include intravenous metronidazole 500 mg every 8 hours plus vancomycin retention enema 500 mg in 100 mL normal saline 4 times daily, with transition to oral vancomycin or fidaxomicin once oral intake is possible 4, 5

Discontinuing the inciting antibiotic as soon as possible reduces recurrence risk, and empiric therapy should be started when substantial laboratory confirmation delay is expected 1, 2
Standard duration of therapy is 10 days, but may need extension to 14 days if response is delayed, and fidaxomicin has been associated with lower recurrence rates compared to vancomycin, particularly after first recurrence 1, 4

Using metronidazole for severe or recurrent CDI is not recommended due to lower cure rates compared to vancomycin, and failing to discontinue the inciting antibiotic increases recurrence risk 1, 3
Administering only intravenous vancomycin for CDI is not effective, and performing a "test of cure" after treatment completion is not recommended 4
Underestimating recurrence risk and using repeated or prolonged courses of metronidazole due to neurotoxicity risk should be avoided 1, 4