What is the treatment for colitis associated with Clostridium difficile?

Treatment of Clostridioides difficile Colitis

Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments for all initial episodes of C. difficile infection, with metronidazole now relegated only to situations where these preferred agents are unavailable. 1, 2, 3

Initial Episode Treatment Algorithm

Non-Severe Disease

• First-line: Oral vancomycin 125 mg four times daily for 10 days 4, 1, 3
• Alternative: Fidaxomicin 200 mg twice daily for 10 days, which offers significantly lower recurrence rates (13.3% vs 24.0%) 4, 1
• Only if vancomycin/fidaxomicin unavailable: Metronidazole 500 mg three times daily for 10 days 4, 1

Non-severe disease is defined as white blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1. The shift away from metronidazole as first-line therapy is based on two randomized controlled trials demonstrating vancomycin's superiority in clinical cure rates 4.

Severe Disease

• First-line: Vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 4, 1, 2
• Consider escalation: Vancomycin 500 mg four times daily for 10 days in very severe cases 4, 1, 2

Severe disease indicators include: white blood cell count >15,000/μL, serum creatinine rise >50% above baseline, fever >38.5°C, hemodynamic instability, signs of peritonitis, ileus, elevated serum lactate, or imaging showing colonic distension, wall thickening, or pericolonic fat stranding 4, 1, 2. Vancomycin demonstrated a 97% cure rate versus 76% for metronidazole in severe disease 1.

Fulminant/Complicated Disease

• High-dose oral vancomycin 500 mg four times daily PLUS IV metronidazole 500 mg every 8 hours 1, 2
• If ileus present: Add vancomycin retention enema (500 mg in 100 mL normal saline every 4-12 hours) via large rectal tube 4
• Alternative route: Vancomycin 500 mg four times daily via nasogastric tube if oral administration impossible 4, 2

Fulminant disease includes hypotension, shock, ileus, or megacolon 4. IV vancomycin alone is ineffective as it is not excreted into the colon 3.

Recurrent Infection Management

First Recurrence

• If metronidazole used initially: Vancomycin 125 mg four times daily for 10 days 4, 2
• If vancomycin used initially: Prolonged tapered/pulsed vancomycin regimen (e.g., 125 mg four times daily for 10-14 days, then twice daily for 1 week, then once daily for 1 week, then every 2-3 days for 2-8 weeks) 4, 2
• Preferred option: Fidaxomicin 200 mg twice daily for 10 days due to significantly lower rates of second recurrence 4, 1, 2

Recurrence occurs in approximately 20% of patients after initial treatment 5, 6, 7. Recurrence is defined as increased stool frequency for two consecutive days with looser stools or new signs of severe colitis, plus microbiological evidence of toxin-producing C. difficile 4.

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen 4, 2
• Alternative: Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 4
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 4, 2
• Highly effective option: Fecal microbiota transplantation (FMT) after multiple recurrences despite appropriate antibiotic therapy, with prevention rates of 70-90% 4, 2

Critical Management Principles

Immediate Actions

• Discontinue the inciting antibiotic immediately if clinically feasible 4, 1, 2
• Avoid antiperistaltic agents and opiates completely as they worsen outcomes and increase complications including toxic megacolon 4, 1, 2
• Stop inducing antibiotics and observe for 48 hours in mild cases only (stool frequency <4 times daily, no signs of severe colitis) 4

Monitoring and Response Assessment

• Assess clinical response by 72 hours: Expect decreased stool frequency or improved consistency 4, 1, 2
• Do NOT perform "test of cure" after treatment completion 1
• Asymptomatic carriage of C. difficile spores can continue for weeks after symptom resolution 4, 5, 6
• In patients >65 years: Monitor renal function during and after treatment due to increased nephrotoxicity risk 3

Surgical Intervention Criteria

Obtain surgical consultation early and perform total abdominal colectomy with ileostomy for: 4, 1, 2

• Perforation of the colon
• Toxic megacolon (radiological distension plus severe systemic inflammatory response)
• Acute abdomen with peritonitis
• Severe ileus with systemic inflammation and deteriorating clinical condition not responding to maximal antibiotic therapy
• Serum lactate >5.0 mmol/L (operate urgently before this threshold is exceeded)

Surgery should be performed before colitis becomes very severe, as mortality increases dramatically with delayed intervention 4, 1. A novel alternative under investigation is diverting loop ileostomy with colonic lavage plus intracolonic antegrade vancomycin and IV metronidazole 4.

Important Caveats

Vancomycin dosing: The 125 mg dose is as effective as 500 mg for non-severe disease, making the lower dose preferred unless the patient is critically ill 4, 6. Higher doses (500 mg) do not improve cure rates in non-severe cases but increase cost 6.

Fidaxomicin exception: Fidaxomicin's advantage in reducing recurrence is lost in patients infected with C. difficile PCR ribotype 027 4.

Systemic absorption risk: Patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of oral vancomycin, requiring monitoring of serum vancomycin levels, especially in those with renal insufficiency or receiving concomitant aminoglycosides 3.

IBD patients: In inflammatory bowel disease patients with CDI, symptoms may overlap with IBD flares, creating diagnostic challenges; repeated testing may be necessary to assess treatment response 4.