What is the recommended treatment for Clostridioides (C.) difficile infections?

Treatment of Clostridioides difficile Infection

For the treatment of Clostridioides difficile infection, oral vancomycin 125 mg four times daily for 10 days is recommended as first-line therapy regardless of disease severity, with fidaxomicin 200 mg twice daily for 10 days as an effective alternative. 1, 2

Treatment Based on Disease Severity

Non-severe CDI

• Oral vancomycin 125 mg four times daily for 10 days is recommended as first-line therapy 1, 2
• Fidaxomicin 200 mg twice daily for 10 days is an effective alternative with lower recurrence rates 1
• Metronidazole 500 mg orally three times daily for 10 days can be considered as an alternative only for non-severe cases, but is no longer preferred due to increasing treatment failures 3, 1
• Mild CDI clearly induced by antibiotics may be treated by stopping the inciting antibiotic with close monitoring for clinical deterioration 3

Severe CDI

• Oral vancomycin 125 mg four times daily for 10 days is the treatment of choice 3, 1
• Fidaxomicin 200 mg twice daily for 10 days is an effective alternative 1
• Criteria for severe CDI include: leukocytosis (WBC >15 × 10^9/L), low serum albumin, rise in serum creatinine (>50% above baseline), or other signs of severe colitis 3, 2

Fulminant CDI

• Vancomycin 500 mg orally four times daily with intravenous metronidazole 500 mg three times daily is recommended 1
• When oral therapy is impossible: metronidazole 500 mg intravenously three times daily plus intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 3
• Early surgical consultation is advised for patients with systemic toxicity, perforation of the colon, or deteriorating clinical condition not responding to antibiotic therapy 3

Treatment of Recurrent CDI

• First recurrence: Treat as an initial episode based on severity, preferably with oral vancomycin 125 mg four times daily for 10 days, especially if metronidazole was used initially 3, 1
• Second and subsequent recurrences: Vancomycin 125 mg four times daily for at least 10 days, with consideration of a taper/pulse strategy (e.g., decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 3
• Fidaxomicin 200 mg twice daily for 10 days may be considered, particularly when vancomycin was used for the first episode 1, 2
• Fecal microbiota transplantation should be considered for patients with multiple recurrent episodes who have received appropriate antibiotic therapy for at least three episodes 4, 5

Important Considerations

• Discontinue the inciting antibiotic as soon as possible to reduce the risk of CDI recurrence 1, 2
• Avoid antiperistaltic agents and opiates as they may worsen outcomes 3, 2
• Oral vancomycin may be replaced by teicoplanin 100 mg twice daily, if available 3
• Vancomycin capsules are indicated specifically for C. difficile-associated diarrhea and must be given orally for this indication 6
• Monitor renal function during and following treatment with oral vancomycin, especially in patients >65 years of age, as nephrotoxicity can occur 6
• Fidaxomicin is associated with lower recurrence rates compared to vancomycin due to its microbiome-sparing properties 7, 8

Pediatric Considerations

• For pediatric patients ≥6 months of age with non-severe CDI: weight-based dosing applies 7
• For children able to swallow tablets and weighing at least 12.5 kg: one 200 mg fidaxomicin tablet twice daily for 10 days 7
• For children using oral suspension: weight-based dosing of fidaxomicin twice daily for 10 days 7
• For vancomycin in pediatric patients: 40 mg/kg/day in 3-4 divided doses (not to exceed 2 g daily) 6

Diagnostic Approach

• Consider CDI in patients with three or more episodes of unexplained, unformed stools in 24 hours who are not taking laxatives 5
• Testing should include enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing 5
• In children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors 5

The treatment landscape for C. difficile infection has evolved significantly, with vancomycin and fidaxomicin now being the cornerstones of therapy, while metronidazole has been relegated to an alternative option only for mild-to-moderate disease in younger patients with few risk factors for recurrence 4, 9.