How should enterotoxigenic Escherichia coli (ETEC) diarrhea be managed in adults (including travelers) and children?

Treatment of ETEC Diarrhea

For adults with ETEC diarrhea, azithromycin (1000 mg single dose or 500 mg daily for 3 days) is the first-line antibiotic, combined with aggressive oral rehydration therapy; however, most cases of uncomplicated traveler's diarrhea do not require antibiotics at all. 1, 2

When to Treat with Antibiotics

Antibiotic therapy is indicated only for:

• Severe diarrhea causing incapacitation or inability to carry out planned activities 1
• Dysentery (bloody diarrhea with fever) 1, 2
• Fever ≥38.5°C with signs of sepsis 2
• Moderate diarrhea in travelers who cannot afford downtime 1

Do NOT use antibiotics for:

• Mild, uncomplicated watery diarrhea 1
• Asymptomatic contacts of infected patients 2
• Most cases of traveler's diarrhea, which are self-limited 1

First-Line Antibiotic Regimen

Azithromycin is superior to all alternatives due to widespread fluoroquinolone resistance in ETEC, particularly in South and Southeast Asia where resistance exceeds 90% 1, 2:

• Single-dose regimen: 1000 mg orally once 1, 2
• 3-day regimen: 500 mg orally once daily for 3 days 1, 2, 3

Both regimens are equally effective; single-dose therapy offers convenience for travelers 1.

Alternative Antibiotics (Second-Line)

Fluoroquinolones may be used only in regions with documented low resistance 1, 2:

• Ciprofloxacin 750 mg single dose or 500 mg twice daily for 3 days 1
• Levofloxacin 500 mg single dose or once daily for 3 days 1

Rifaximin (200 mg three times daily for 3 days) is effective for non-invasive ETEC but should NOT be used if fever, bloody stools, or invasive pathogens are suspected 1, 4. The FDA label explicitly states rifaximin is only for noninvasive E. coli strains 4.

Adjunctive Therapy

Loperamide significantly reduces symptom duration and can be combined with antibiotics 1:

• Initial dose: 4 mg orally
• Maintenance: 2 mg after each loose stool (maximum 16 mg/24 hours) 1

Critical contraindication: Do NOT use loperamide if dysentery, high fever, or bloody stools are present 1.

Rehydration: The Cornerstone of Treatment

Oral rehydration solution (ORS) is mandatory for all patients, regardless of antibiotic use 2:

• Use reduced osmolarity ORS containing 50-90 mEq/L sodium 2
• Intravenous fluids are required for severe dehydration, shock, altered mental status, or ileus 2
• Dehydration is the primary cause of diarrhea-related mortality 1

Pediatric Considerations

For children:

• Infants <3 months: Use third-generation cephalosporin, NOT azithromycin 2
• Children ≥12 years: Azithromycin 500 mg daily for 3 days 2
• Loperamide is contraindicated in children <2 years 1

Treatment Duration

Standard duration is 3 days for moderate to severe ETEC diarrhea 1, 3. Single-dose therapy is acceptable for mild-to-moderate cases 1, 3. Antibiotics reduce symptom duration from 50-93 hours to 16-30 hours 1, 2.

When NOT to Test or Treat

Diagnostic testing is NOT recommended for uncomplicated traveler's diarrhea 1. Testing should only be performed if:

• Diarrhea persists ≥14 days (evaluate for parasites) 1
• Fever with bloody stools (rule out Shigella, Salmonella, Campylobacter) 1
• Recent antibiotic use within 8-12 weeks (test for C. difficile) 1

Critical Pitfalls to Avoid

Never use antibiotics empirically for bloody diarrhea without ruling out STEC (Shiga toxin-producing E. coli), as antibiotics increase the risk of hemolytic uremic syndrome 1, 2. Obtain stool culture and Shiga toxin testing first 1.

Do not use fluoroquinolones as first-line therapy in travelers to South Asia, Southeast Asia, or India due to resistance rates exceeding 90% 1, 2.

Reassess patients who fail to improve within 48-72 hours for antibiotic resistance, inadequate rehydration, non-infectious causes, or need for hospitalization 2.