What are the recommended antibiotics for treating infectious colitis, including C. difficile infection?

Antibiotic Treatment for Colitis

Primary Recommendation

For C. difficile colitis, use oral vancomycin 125 mg four times daily for 10 days as first-line therapy for both non-severe and severe disease, based on current guidelines that have moved away from metronidazole due to superior efficacy. 1, 2

Disease Severity Classification

Non-severe C. difficile colitis is characterized by:

• Stool frequency <4 times daily 1, 2
• White blood cell count ≤15,000 cells/μL 3
• Serum creatinine <1.5 mg/dL 3
• Absence of systemic signs of severe disease 4

Severe C. difficile colitis includes any of the following:

• Temperature >38.5°C with rigors 2
• Hemodynamic instability or septic shock 3
• Leukocyte count >15 × 10⁹/L or band neutrophils >20% 4, 1
• Serum creatinine rise >50% above baseline 4, 2
• Elevated serum lactate 4, 2
• Pseudomembranous colitis on endoscopy 4, 2
• Colonic wall thickening or distension on imaging 4, 2
• Signs of peritonitis, ileus, or absent stool passage 4, 3

Treatment Algorithm for Initial Episode

Non-Severe Disease

First-line: Oral vancomycin 125 mg four times daily for 10 days 1, 2, 5

Alternative (less preferred): Oral metronidazole 500 mg three times daily for 10 days 4, 1, 2

• Note: Metronidazole has been relegated to alternative status in recent guidelines due to vancomycin's superior efficacy 3
• May still be considered for outpatients with mild first episodes 6

Another alternative: Fidaxomicin 200 mg twice daily for 10 days, especially for patients at high risk of recurrence 2

Severe Disease

First-line: Oral vancomycin 125 mg four times daily for 10 days 4, 1, 5

Alternative: Fidaxomicin 200 mg twice daily for 10 days 2

Fulminant Disease (with hypotension, shock, ileus, or megacolon)

Recommended regimen: 3, 2

• High-dose oral vancomycin 500 mg four times daily PLUS
• Intravenous metronidazole 500 mg every 8 hours PLUS
• If ileus present: Rectal vancomycin 500 mg in 100 mL normal saline every 4-12 hours as retention enema 4, 3, 2

Critical caveat: Parenteral vancomycin is NOT effective for C. difficile colitis as it is not excreted into the colon 1, 5

Treatment of Recurrent C. difficile Infection

First Recurrence

Treat based on severity using the same approach as initial episode 4, 2

• Consider fidaxomicin 200 mg twice daily for 10 days OR vancomycin in tapered/pulsed regimen 2

Second and Subsequent Recurrences

Recommended: Oral vancomycin 125 mg four times daily for at least 10 days, followed by a taper/pulse strategy 4, 1, 2

Example taper regimen: Decrease daily dose by 125 mg every 3 days 4

Example pulse regimen: 125 mg every 3 days for 3 weeks 4

For multiple recurrences unresponsive to antibiotics: Fecal microbiota transplantation (FMT) with 70-90% success rates 1, 2, 6

Alternative Antibiotic Option

Teicoplanin 100 mg twice daily can replace oral vancomycin if available, particularly in regions where this agent is accessible 4, 1

Critical Management Principles

Discontinue the inciting antibiotic immediately if the colitis was clearly induced by antibiotic use 4, 1, 2

• In mild cases with stool frequency <4 times daily, stopping the antibiotic alone may be sufficient with close observation 4, 1

Avoid antiperistaltic agents (loperamide, diphenoxylate) and opiates as they can precipitate toxic megacolon and worsen outcomes by promoting toxin retention 4, 1, 3

Narrow antibiotic spectrum when possible based on culture results to minimize further disruption of gut flora 4, 1

Surgical Intervention Criteria

Colectomy should be performed urgently for: 4, 1, 2

• Perforation of the colon
• Toxic megacolon
• Severe ileus with deteriorating clinical condition
• Systemic inflammation not responding to antibiotic therapy
• Serum lactate exceeding 5.0 mmol/L

Timing is critical: Surgery should be performed before colitis becomes very severe, as early colectomy improves outcomes 1, 2

Special Monitoring Considerations

Monitor serum vancomycin concentrations in patients with: 5

• Renal insufficiency
• Inflammatory disorders of intestinal mucosa (increased systemic absorption)
• Concomitant aminoglycoside therapy
• Age >65 years

Monitor renal function during and after treatment in patients >65 years of age, as nephrotoxicity risk is increased 5

Common Pitfalls to Avoid

Do not use parenteral vancomycin for C. difficile colitis—it is not excreted into the colon and is ineffective 1, 5

Do not repeat stool testing after treatment to assess response; clinical improvement (decreased stool frequency, improved consistency) is the primary measure of success 1

Do not delay surgery in severe cases waiting for antibiotic response; early intervention saves lives 1, 2

Do not assume all antibiotic-associated diarrhea is C. difficile—confirm diagnosis with stool toxin testing or endoscopy before treating 1

Do not use metronidazole for severe CDI as it has higher failure rates compared to vancomycin 2