What is the recommended treatment for a patient with confirmed Clostridioides difficile colitis, including initial therapy, management of severe disease, and recurrence prevention?

Treatment of Clostridioides difficile Colitis

Oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for initial C. difficile infection, with fidaxomicin 200 mg twice daily for 10 days as an equally effective alternative. 1, 2, 3

Immediate Management Steps

Stop the inciting antibiotic immediately if clinically feasible, as this alone resolves symptoms in approximately 25% of mild cases and continued antibiotic use significantly increases recurrence risk. 1, 3 If ongoing antibiotic therapy is required for another infection, switch to agents less frequently implicated in CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline. 1, 4

Avoid antiperistaltic agents and opiates completely, as these promote toxin retention, worsen outcomes, and increase the risk of toxic megacolon. 3

Treatment Algorithm Based on Disease Severity

Non-Severe Disease

• Definition: Stool frequency <4 times daily, WBC ≤15,000/μL, serum creatinine <1.5 mg/dL 2, 3
• Treatment: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1, 2
• Critical caveat: Metronidazole is no longer recommended as first-line therapy and should only be used when vancomycin or fidaxomicin are unavailable 1

Severe Disease

• Definition: WBC >15,000/μL OR serum creatinine ≥1.5 mg/dL 4, 2
• Treatment: Oral vancomycin 125 mg four times daily for 10 days (doses up to 500 mg four times daily have been used in severe cases) 4, 2
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

Fulminant Disease

• Definition: Hypotension, shock, ileus, toxic megacolon, or serum lactate >5.0 mmol/L 4, 3
• Treatment regimen:
  • Oral vancomycin 500 mg four times daily 4, 3
  • PLUS IV metronidazole 500 mg every 8 hours 3, 5
  • PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours via retention enema if ileus present 2, 3
  • Consider vancomycin 500 mg four times daily via nasogastric tube if oral route impossible 3

Monitoring and Treatment Response

Assess clinical response by 72 hours, as treatment failure is defined as absence of improvement in stool frequency or consistency after 3 days. 1, 2 Monitor stool output, white blood cell count, and C-reactive protein to gauge treatment response. 4

Rising WBC count ≥25,000/μL or lactate ≥5 mmol/L indicates potential need for surgical intervention. 2, 3

Surgical Intervention

Obtain early surgical consultation when clinical deterioration continues despite antibiotics, as early surgery improves survival. 3

Indications for urgent colectomy: 3

• Colonic perforation
• Toxic megacolon or severe ileus
• Systemic inflammation with deteriorating clinical condition despite maximal medical therapy
• Serum lactate >5.0 mmol/L

Diverting loop ileostomy with colonic lavage is emerging as a viable alternative to total abdominal colectomy. 4, 6

Fecal Microbiota Transplantation in Severe/Fulminant Disease

FMT should be considered in hospitalized patients not responding to standard antibiotic therapy, generally within 2-5 days after initiating CDI treatment. 4

FMT administration in severe disease: 4

• First dose via colonoscopy or flexible sigmoidoscopy (allows confirmation of diagnosis and severity assessment)
• Avoid nasoenteric tube administration due to increased aspiration risk
• Most patients with severe/fulminant CDI will need repeat FMT every 3-5 days based on treatment response
• Continue anti-CDI antibiotics during and after FMT
• After resolution, continue suppressive vancomycin at discharge and perform final fecal microbiota-based therapy as outpatient to prevent recurrence

Contraindications to FMT: bowel perforation, obstruction, or severe immunocompromise 4

Recurrent CDI Management

Approximately 25% of patients will experience at least one recurrence. 1, 2

First recurrence: Treat the same as initial episode with oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 3

Second and subsequent recurrences: 3

• Taper/pulse vancomycin strategy: decrease daily dose by 125 mg every 3 days, then pulse dosing (125 mg every 3 days for 3 weeks)
• FMT should be considered for all patients with recurrent CDI, as this has been shown to be safe and effective 7

Critical Pitfalls to Avoid

Never use repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity. 4, 1, 3

Discontinue unneeded proton pump inhibitors, as there is a clinical association between PPI use and CDI, though stewardship activities are more important than blanket discontinuation. 4

Infection Control

Use soap and water for hand hygiene, NOT alcohol-based sanitizers, as alcohol does not kill C. difficile spores or remove them from hands. 4, 1

Implement contact precautions and ensure thorough environmental cleaning and disinfection. 1