What are the appropriate antibiotic regimens for the different etiologies of colitis (Clostridioides difficile, Campylobacter jejuni, Shigella, Salmonella, and enterohemorrhagic Escherichia coli) and when are antibiotics contraindicated?

Antibiotic Management of Infectious Colitis by Etiology

Clostridioides difficile Infection (CDI)

For non-severe CDI, treat with oral metronidazole 500 mg three times daily for 10 days; for severe CDI, use oral vancomycin 125 mg four times daily for 10 days. 1, 2

Disease Severity Classification

Non-severe CDI is defined by: 1, 2

• Stool frequency <4 times daily
• White blood cell count <15 × 10⁹/L
• Absence of systemic inflammatory signs

Severe CDI includes any of the following: 3, 2

• Fever >38.5°C with rigors
• Hemodynamic instability or septic shock
• Signs of peritonitis (rebound tenderness, guarding, decreased bowel sounds)
• Ileus (vomiting, absent stool passage)
• Marked leukocytosis (WBC >15 × 10⁹/L) or left shift (>20% bands)
• Serum creatinine rise >50% above baseline
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Colonic wall thickening or distension on imaging

First-Line Treatment Algorithm

Initial episode - oral therapy possible: 3, 1, 2

• Non-severe: Metronidazole 500 mg three times daily orally for 10 days (A-I evidence)
• Severe: Vancomycin 125 mg four times daily orally for 10 days (A-I evidence)

Initial episode - oral therapy impossible: 3

• Non-severe: Metronidazole 500 mg three times daily intravenously for 10 days
• Severe: Metronidazole 500 mg three times daily IV PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube

Recurrent CDI Management

First recurrence: Treat the same as initial episode based on severity (metronidazole for non-severe, vancomycin for severe). 2

Second and subsequent recurrences: 3, 1, 2

• Vancomycin 125 mg four times daily orally for at least 10 days, followed by taper/pulse strategy (decreasing daily dose by 125 mg every 3 days, or 125 mg every 3 days for 3 weeks)
• Alternative: Fidaxomicin 200 mg twice daily for 10 days (B-II evidence)
• For multiple recurrences unresponsive to antibiotics: Fecal microbiota transplantation (FMT) with 70-90% success rates (A-I evidence) 1, 2

Critical Management Principles

Avoid the following: 3, 4, 2

• Antiperistaltic agents (loperamide, diphenoxylate) and opiates—these can precipitate toxic megacolon
• Repeat stool testing after treatment—clinical improvement is the primary measure of success
• Parenteral vancomycin—it is not excreted into the colon and is ineffective

Discontinue inciting antibiotics immediately if possible. 3, 2 If continued antibiotic therapy is required for another infection, use agents less frequently associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline. 3

Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity. 3

Surgical Intervention

Colectomy should be performed urgently for: 3, 2

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

Surgery should be performed before colitis becomes very severe to improve outcomes. 3, 2

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Campylobacter jejuni, Shigella, and Salmonella

For febrile dysenteric diarrhea caused by invasive bacterial enteropathogens (Shigella, Salmonella, Campylobacter), treat empirically with azithromycin 1000 mg as a single dose in adults. 5

When to Treat

Antibiotics should be initiated for: 5, 6

• All confirmed cases of Shigella, Salmonella, and Campylobacter once laboratory diagnosis is made
• High-risk patients (immunocompromised, elderly, those with prosthetic devices)
• Patients with complicated disease (severe symptoms, systemic involvement)
• Empiric treatment when febrile dysentery is present before culture results

Diagnostic Approach

Standard stool culture should be performed in all patients with infectious colitis. 5 Infectious colitis is diagnosed when diarrhea is accompanied by: 5

• Fever and/or dysentery
• Stools containing inflammatory markers (leukocytes, lactoferrin, calprotectin)
• Positive stool culture for invasive bacterial enteropathogen
• Colonic inflammation by endoscopy

Clinical Presentation

These bacterial pathogens cause inflammatory-type diarrhea characterized by bloody, purulent, and mucoid stool, with associated fever, tenesmus, and severe abdominal pain. 6

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Enterohemorrhagic Escherichia coli (EHEC/STEC)

Antibiotics are CONTRAINDICATED in enterohemorrhagic E. coli (STEC) infection, including E. coli O157:H7. 5

Diagnostic Clues

Suspect STEC when: 5

• Acute dysentery with only low-grade fever or no fever (unlike other bacterial causes)
• Bloody diarrhea without high fever

When STEC is suspected, a competent laboratory should look for E. coli O157:H7 and Shiga toxin directly in stool. 5

Why Antibiotics Are Contraindicated

Antibiotic use in STEC infection increases the risk of hemolytic uremic syndrome (HUS) by promoting release of Shiga toxin from bacterial lysis. Treatment is supportive only.

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Common Pitfalls and Caveats

Do not assume all antibiotic-associated diarrhea is C. difficile—confirm diagnosis with stool toxin testing or endoscopy before treating. 2

Do not delay surgery in severe CDI waiting for antibiotic response—early colectomy improves outcomes when lactate exceeds 5.0 mmol/L or when there is clinical deterioration despite antibiotics. 3, 2

Do not use antibiotics for STEC/EHEC—this is the single most important contraindication in infectious colitis management due to increased HUS risk. 5

Epidemiologic clues guide specialized testing: 5

• International travel
• Shellfish-associated diarrhea
• Living in parasite-endemic regions

Although many bacterial colitis infections are self-limiting, antibiotics should be used for high-risk patients and those with complicated disease. 6