What is the recommended treatment for a patient with confirmed Clostridioides (C.) difficile infection presenting with 2 weeks of diarrhea, nausea, and vomiting?

Treatment of Confirmed Clostridioides difficile Infection

For this patient with confirmed C. difficile infection presenting with 2 weeks of symptoms, oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days is the recommended first-line treatment. 1, 2

Immediate Management Steps

Discontinue Inciting Antibiotics

• Stop any ongoing antibiotic therapy as soon as possible, as continued use significantly increases the risk of treatment failure and recurrence 1, 3
• If antibiotics must be continued for another infection, switch to agents less associated with CDI (aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline) 1, 4

Assess Disease Severity

Before initiating treatment, determine if this is non-severe or severe CDI:

Non-severe CDI criteria: 2, 3

• White blood cell count ≤15,000 cells/mL
• Serum creatinine <1.5 mg/dL
• Stool frequency <4 times daily
• No signs of severe colitis

Severe CDI criteria: 1, 2, 3

• White blood cell count ≥15,000 cells/mL
• Serum creatinine >1.5 mg/dL (or rise >50% above baseline)
• Fever >38.5°C
• Hemodynamic instability or signs of septic shock
• Signs of peritonitis (abdominal tenderness, rebound, guarding)
• Ileus or toxic megacolon

First-Line Treatment Algorithm

For Non-Severe CDI (Most Likely in This Case)

Primary recommendation: 1, 2

• Oral vancomycin 125 mg four times daily for 10 days, OR
• Oral fidaxomicin 200 mg twice daily for 10 days

Alternative (only if vancomycin/fidaxomicin unavailable): 1

• Oral metronidazole 500 mg three times daily for 10 days
• Important caveat: Metronidazole is inferior to vancomycin, with lower cure rates especially in severe disease (76% vs 97%) 1
• Never use repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

For Severe CDI

Primary recommendation: 1

• Oral vancomycin 125 mg four times daily for 10 days
• Vancomycin demonstrates 97% cure rate in severe disease compared to 76% for metronidazole 1

For Fulminant CDI (if present)

If signs of fulminant disease develop: 1, 2

• Oral vancomycin 500 mg four times daily, PLUS
• Intravenous metronidazole 500 mg every 8 hours
• If ileus present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1, 2

Key Evidence Supporting Vancomycin/Fidaxomicin Over Metronidazole

The 2018 IDSA/SHEA guidelines represent a major shift from previous recommendations: 1

• Randomized controlled trials since 2000 consistently show vancomycin superiority over metronidazole
• In one pivotal study of 150 patients, vancomycin achieved 97% cure vs 84% for metronidazole (p<0.006) 1
• For severe disease specifically, vancomycin achieved 97% cure vs 76% for metronidazole (p=0.02) 1
• Fidaxomicin shows similar initial cure rates to vancomycin but significantly lower recurrence rates (19.7% vs 35.5%) 4

Supportive Care Measures

What to Avoid

• Never use antimotility agents (loperamide) or opiates - these can worsen outcomes and mask symptoms 1, 3, 4
• Discontinue proton pump inhibitors if not medically necessary - associated with increased CDI risk and recurrence 1, 4

Supportive Interventions

• Provide intravenous fluid replacement for volume depletion 4
• Replace electrolytes as needed 4
• Consider albumin supplementation if severe hypoalbuminemia present 4

Special Considerations for This Patient

Given the 2-week duration of symptoms, this patient has already been symptomatic for an extended period:

• Ensure the patient can tolerate oral medications (presence of vomiting is concerning) 1
• If vomiting prevents oral intake, consider hospitalization for IV metronidazole plus rectal vancomycin 1
• Monitor closely for signs of clinical deterioration or development of severe/fulminant disease 1

Monitoring Treatment Response

Expected response: 1, 3

• Stool frequency should decrease or consistency improve within 3 days
• No new signs of severe colitis should develop

Treatment failure defined as: 1

• Absence of improvement after 3 days
• Development of new signs of severe colitis

Common Pitfalls to Avoid

1. Do not use metronidazole as first-line when vancomycin/fidaxomicin are available - this represents outdated practice 1, 2
2. Do not continue inciting antibiotics unnecessarily - this is the single most important modifiable risk factor 1, 3
3. Do not prescribe antimotility agents - historically associated with bad outcomes 1, 3
4. Do not use repeated courses of metronidazole - cumulative neurotoxicity risk 1
5. Do not delay treatment while awaiting test results if severe disease suspected - empiric therapy is appropriate 1