What antibiotics are indicated for the treatment of infectious colitis, specifically Clostridioides difficile (C. diff) colitis?

Antibiotic Treatment for Infectious Colitis

For non-severe Clostridioides difficile colitis, oral metronidazole 500 mg three times daily for 10 days is the first-line treatment, while severe C. difficile colitis requires oral vancomycin 125 mg four times daily for 10 days. 1, 2

Disease Severity Classification

Determining disease severity is critical for selecting appropriate antibiotic therapy:

Non-severe C. difficile colitis is characterized by:

• Stool frequency less than 4 times daily 3, 1
• White blood cell count less than 15 × 10⁹/L 1
• Absence of systemic signs of severe disease 1

Severe C. difficile colitis includes any of the following:

• Temperature greater than 38.5°C with rigors 3, 2
• Hemodynamic instability or signs of septic shock 3, 1
• Signs of peritonitis (decreased bowel sounds, abdominal tenderness, rebound tenderness, guarding) 3
• Signs of ileus (vomiting, absent passage of stool) 3, 2
• Marked leukocytosis (white blood cell count greater than 15 × 10⁹/L) 3, 1
• Marked left shift (band neutrophils greater than 20% of leukocytes) 3
• Rise in serum creatinine greater than 50% above baseline 3, 2
• Elevated serum lactate 3, 2
• Pseudomembranous colitis on endoscopy 3, 2
• Colonic distension or wall thickening on imaging 3, 2

First-Line Antibiotic Treatment Algorithm

For Non-Severe C. difficile Colitis (Oral Therapy Possible):

• Metronidazole 500 mg orally three times daily for 10 days 3, 1, 2
• This is the preferred first-line agent based on strong evidence (A-I recommendation) 3, 1

For Severe C. difficile Colitis (Oral Therapy Possible):

• Vancomycin 125 mg orally four times daily for 10 days 3, 1, 2, 4
• This is the preferred first-line agent for severe disease based on strong evidence (A-I recommendation) 3, 1
• Fidaxomicin 200 mg twice daily for 10 days is an alternative, especially for patients at high risk of recurrence 2

When Oral Therapy is Impossible:

For non-severe disease:

• Metronidazole 500 mg intravenously three times daily for 10 days 3

For severe disease:

• Metronidazole 500 mg intravenously three times daily for 10 days PLUS 3
• Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours as retention enema 3 AND/OR
• Vancomycin 500 mg four times daily by nasogastric tube 3

For fulminant disease with ileus:

• Oral vancomycin 500 mg four times daily for 10 days PLUS 2
• Intravenous metronidazole 500 mg every 8 hours 2
• Rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 2

Treatment of Recurrent C. difficile Infection

First recurrence:

• Treat the same as the initial episode based on severity (metronidazole for non-severe, vancomycin for severe) 3, 1

Second and subsequent recurrences:

• Vancomycin 125 mg orally four times daily for at least 10 days 3, 1
• Consider a taper/pulse strategy (e.g., decreasing daily dose by 125 mg every 3 days, or 125 mg every 3 days for 3 weeks) 3, 1
• Fidaxomicin 200 mg twice daily for 10 days is an alternative 1
• Fecal microbiota transplantation (FMT) is strongly recommended for multiple recurrences unresponsive to antibiotics, with 70-90% success rates 1, 2

Alternative Antibiotic Options

• Teicoplanin 100 mg twice daily can replace oral vancomycin if available 3, 1

Critical Management Principles

Discontinue inciting antibiotics immediately:

• In mild C. difficile colitis clearly induced by antibiotic use, stopping the inciting antibiotic may be sufficient 3, 1
• Observe patients closely for clinical deterioration and initiate treatment immediately if this occurs 3

Avoid medications that worsen colitis:

• Antiperistaltic agents (loperamide, diphenoxylate) and opiates must be avoided, as they can precipitate toxic megacolon 3, 1

Narrow antibiotic spectrum when possible:

• Use antibiotics covering a spectrum no broader than necessary 3
• Narrow the antibiotic spectrum after culture and susceptibility results become available 3

Surgical Intervention Criteria

Colectomy should be performed urgently for:

• Perforation of the colon 3, 1
• Toxic megacolon 1, 2
• Severe ileus 3, 2
• Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy 3, 1
• Surgery should preferably be performed before serum lactate exceeds 5.0 mmol/L 3, 1

Common Pitfalls to Avoid

Do not use parenteral vancomycin for C. difficile colitis:

• Intravenous vancomycin is not excreted into the colon and is completely ineffective for treating C. difficile colitis 1, 4
• Oral vancomycin must be used for colonic infections 4

Do not repeat stool testing after treatment:

• Clinical improvement (decreased stool frequency, improved consistency) is the primary measure of treatment success 3
• Microbiological testing should not be used to assess response 1

Do not delay surgery in severe cases:

• Early colectomy improves outcomes in patients with fulminant disease 1
• Waiting for antibiotic response in deteriorating patients increases mortality 1

Do not assume all antibiotic-associated diarrhea is C. difficile:

• Confirm diagnosis with stool toxin testing or endoscopy before treating 1
• Consider alternative diagnoses including inflammatory bowel disease if symptoms persist despite appropriate therapy 5

Monitor for systemic absorption in high-risk patients:

• Patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of oral vancomycin 4
• Monitor serum vancomycin concentrations in patients with renal insufficiency, colitis, or those receiving concomitant aminoglycoside therapy 4

Monitor renal function in elderly patients:

• Nephrotoxicity risk is increased in patients greater than 65 years of age 4
• Renal function should be monitored during and following treatment with oral vancomycin in elderly patients 4