What antibiotics should I use to treat infective diarrhea?

Antibiotic Selection for Infective Diarrhea

First-Line Empiric Antibiotic Choice

For adults with infectious diarrhea requiring antibiotics, azithromycin (500 mg single dose for watery diarrhea, or 1000 mg single dose for dysentery/febrile diarrhea) is the preferred first-line agent, with fluoroquinolones reserved as second-line due to widespread resistance, particularly among Campylobacter species. 1, 2

When to Use Antibiotics (Indications)

Antibiotics are not routinely recommended for most infectious diarrhea, but should be given in these specific situations:

• Infants <3 months of age with suspected bacterial etiology 1, 3
• Fever, abdominal pain, bloody diarrhea suggesting bacillary dysentery (presumptive Shigella) 1, 4
• Recent international travelers with fever ≥38.5°C and/or signs of sepsis 1, 4
• Immunocompromised patients with severe illness and bloody diarrhea 1, 4
• Suspected enteric fever with clinical features of sepsis 1, 4

Specific Antibiotic Recommendations by Pathogen

Shigella Species

• Azithromycin is first-line: 500 mg twice daily for 3 days (or single 1000 mg dose for dysentery) 5, 1
• Alternative: Ceftriaxone 100 mg/kg/day if confirmed Shigella infection 5
• Fluoroquinolones (ciprofloxacin 500 mg twice daily for 3 days) only if susceptible 5
• TMP-SMZ (160/800 mg twice daily for 3 days) only if documented susceptibility 5

Campylobacter Species

• Azithromycin 500 mg daily for 3 days is preferred due to >90% fluoroquinolone resistance in many regions 1, 2
• Erythromycin 500 mg twice daily for 5 days is an alternative 5
• Fluoroquinolones should be avoided due to widespread resistance 1, 2

Cholera (Vibrio cholerae)

• Azithromycin single dose is superior to ciprofloxacin, reducing diarrhea duration by >1 day 1
• Alternative: Doxycycline 300 mg single dose or tetracycline 500 mg four times daily for 3 days 5
• TMP-SMZ should be avoided as it is less effective than doxycycline 5

Non-Typhoidal Salmonella

• Antibiotics are not routinely recommended for immunocompetent patients 5, 1
• Treat only if: severe infection, age <6 months or >50 years, prosthetic devices, valvular heart disease, severe atherosclerosis, malignancy, or uremia 5, 1
• When indicated: Ciprofloxacin 500 mg twice daily for 5-7 days (if susceptible), ceftriaxone 100 mg/kg/day, or azithromycin 5, 1

Enterotoxigenic E. coli (ETEC)

• Azithromycin 1000 mg single dose or 500 mg daily for 3 days 1, 2
• Alternative: Ciprofloxacin 500 mg twice daily for 3 days (if susceptible) 5, 6
• Rifaximin 200 mg three times daily for 3 days (only for non-invasive diarrhea) 1, 2

Clostridioides difficile

• Metronidazole 250-500 mg three to four times daily for 10 days 5
• Oral vancomycin for severe cases 5

Critical Contraindications

NEVER give antibiotics for STEC O157:H7 or Shiga toxin 2-producing E. coli as this significantly increases the risk of hemolytic uremic syndrome 1, 3, 4

• Asymptomatic contacts should not receive antibiotics 1, 4
• Avoid antimotility agents (loperamide) in children <18 years 4

Pediatric-Specific Recommendations

• Infants <3 months: Third-generation cephalosporin (ceftriaxone) is preferred 1, 3
• Children >3 months: Azithromycin based on local susceptibility patterns and travel history 1, 3
• Children with neurologic involvement: Third-generation cephalosporin 1

Geographic Considerations

The choice between azithromycin and fluoroquinolones depends critically on travel history:

• Southeast Asia and India: Azithromycin is mandatory due to >90% fluoroquinolone resistance in Campylobacter 1, 2
• Thailand: Fluoroquinolone resistance exceeds 90%, making azithromycin superior 1
• Regions with documented low resistance: Fluoroquinolones may be considered as second-line 1

Practical Treatment Algorithm

1. Assess severity: Check for fever ≥38.5°C, bloody stools, signs of sepsis, dehydration status 1, 4
2. Determine risk factors: Age (<3 months or >50 years), immunocompromised status, recent international travel 1, 4
3. Obtain stool culture if considering antibiotics, especially for bloody diarrhea 1
4. Start rehydration immediately with oral rehydration solution (50-90 mEq/L sodium) for all patients 1, 4
5. If antibiotics indicated:
   • First-line: Azithromycin 500 mg (watery) or 1000 mg (dysentery) single dose 1, 2
   • Second-line: Ciprofloxacin 750 mg single dose or 500 mg twice daily for 3 days (only if low local resistance) 1, 2
   • Pediatric <3 months: Ceftriaxone 1, 3
6. Modify therapy once culture results available 1, 4

Common Pitfalls to Avoid

• Overuse of fluoroquinolones: The FDA has issued safety warnings about fluoroquinolones; they should only be used when no more appropriate options are available 5, 1
• Treating STEC with antibiotics: This increases hemolytic uremic syndrome risk 1, 3
• Neglecting rehydration: Rehydration is the cornerstone of management regardless of antibiotic use 1, 4
• Ignoring geographic resistance patterns: Fluoroquinolone resistance in Campylobacter exceeds 90% in many regions 1, 2
• Treating non-typhoidal Salmonella routinely: Only treat high-risk patients 5, 1

Reassessment and Follow-Up

• Reassess within 48-72 hours if no improvement: consider antibiotic resistance, fluid/electrolyte imbalances, or non-infectious causes 1
• Symptoms lasting ≥14 days: Consider non-infectious causes (inflammatory bowel disease, lactose intolerance) 1, 4
• Modify or discontinue antibiotics when specific pathogen identified 1, 4