What is the role of Azithromycin (a macrolide antibiotic) in treating acute gastroenteritis in adults, particularly those with suspected bacterial causes or at high risk for complications?

Azithromycin for Acute Gastroenteritis

Azithromycin should NOT be used routinely in acute gastroenteritis in adults, as most cases are viral and self-limited; however, it is the first-line antibiotic when bacterial treatment is indicated—specifically for dysentery (bloody diarrhea with fever), suspected Shigella or Campylobacter infection, travelers' diarrhea with high fever, or in immunocompromised patients with severe illness. 1

When Azithromycin IS Indicated

Dysentery and Bloody Diarrhea

• Azithromycin is the first-line empiric antibiotic for adults with dysentery (frequent bloody stools, fever, abdominal cramps, tenesmus) presumptively due to Shigella or other invasive bacterial pathogens 1
• Dosing: 500 mg daily for 3 days or single 1-gram dose 1
• Azithromycin has demonstrated superior efficacy to fluoroquinolones in settings with high fluoroquinolone-resistant Campylobacter (>90% resistance rates in Thailand and increasingly worldwide) 1

Travelers' Diarrhea

• Azithromycin is recommended as first-line therapy for travelers' diarrhea with fever ≥38.5°C and/or signs of sepsis, particularly when returning from regions with high fluoroquinolone resistance 1
• Azithromycin demonstrates equivalent efficacy to fluoroquinolones for watery diarrhea and superior efficacy for dysentery 1
• Single-dose regimens (1 gram) are acceptable and improve adherence 1

Specific Pathogens

• Shigella infections should be treated promptly with azithromycin as the preferred agent due to demonstrated efficacy and favorable resistance patterns 1, 2, 3
• Campylobacter jejuni infections warrant azithromycin treatment when diagnosed early (within 72 hours of symptom onset), particularly in severe cases 1, 2, 3
• Severe Salmonella infections in high-risk patients may require treatment, though ciprofloxacin or ceftriaxone are preferred over azithromycin 2, 3

High-Risk Populations

• Immunocompromised adults with severe illness and bloody diarrhea should receive empiric antibacterial treatment, with azithromycin being an appropriate choice 1
• Infants <3 months with suspected bacterial etiology require empiric treatment, though third-generation cephalosporins are preferred in this age group 1

When Azithromycin Is NOT Indicated

Routine Acute Gastroenteritis

• Empiric antimicrobial therapy is NOT recommended for immunocompetent adults with acute watery diarrhea without recent international travel 1, 4
• Most acute gastroenteritis (approximately 70%) is viral in origin, rendering antibiotics ineffective 5
• The primary treatment for acute gastroenteritis is oral rehydration solution (ORS), not antibiotics 1, 6, 4

Specific Contraindications

• Antibiotics should be avoided in STEC O157 and other Shiga toxin 2-producing E. coli infections due to increased risk of hemolytic uremic syndrome 1, 4
• Uncomplicated Salmonella gastroenteritis in healthy hosts does not require antibiotic treatment 7
• Asymptomatic contacts of patients with bloody diarrhea should not receive empiric treatment 1

Clinical Decision Algorithm

Step 1: Assess Severity and Clinical Features

• Evaluate for dysentery: bloody stools + fever + abdominal cramps + tenesmus 1
• Check travel history: recent international travel to high-risk regions 1
• Assess immune status: immunocompromised, transplant recipient, cancer patient 1
• Document fever: temperature ≥38.5°C in medical setting 1

Step 2: Determine Need for Empiric Treatment

• Start azithromycin empirically if:
  • Dysentery syndrome present 1
  • Recent international travel + fever ≥38.5°C or sepsis signs 1
  • Immunocompromised with severe illness and bloody diarrhea 1
• Do NOT start antibiotics if:
  • Watery diarrhea without fever in immunocompetent patient 1
  • No recent travel and mild-moderate symptoms 1
  • Suspected viral etiology 5

Step 3: Modify Based on Culture Results

• Discontinue or modify antibiotics when organism identified 1, 4
• Continue azithromycin if Shigella or Campylobacter confirmed 2, 3
• Switch to pathogen-specific therapy if other bacteria identified 1
• Stop antibiotics if viral pathogen or no pathogen identified 4

Dosing Regimens

Adults

• Standard: 500 mg orally daily for 3 days 1
• Single-dose: 1 gram orally as single dose 1
• Both regimens demonstrate comparable efficacy; single-dose improves adherence 1

Children

• Azithromycin is preferred over fluoroquinolones in pediatric patients based on local susceptibility patterns and travel history 1
• Specific pediatric dosing should follow weight-based calculations 2, 3

Common Pitfalls to Avoid

• Do not prescribe azithromycin for routine watery diarrhea without specific indications—this promotes antimicrobial resistance and provides no benefit 1, 4
• Do not use fluoroquinolones as first-line for dysentery—azithromycin is superior due to widespread fluoroquinolone resistance in Campylobacter and emerging resistance in Shigella 1
• Do not continue antibiotics "to complete the course" when no bacterial pathogen is identified—this is poor antimicrobial stewardship 4
• Do not give antibiotics for suspected STEC infections—this increases risk of hemolytic uremic syndrome 1, 4
• Do not delay rehydration while awaiting culture results—ORS is the cornerstone of treatment regardless of etiology 1, 6

Key Nuances

The evidence strongly supports azithromycin as first-line therapy specifically for dysentery and travelers' diarrhea with fever, representing a shift from historical fluoroquinolone preference due to emerging resistance patterns 1. The 2017 IDSA guidelines 1 and travelers' diarrhea guidelines 1 both emphasize restricting empiric antibiotic use to specific clinical scenarios, reflecting antimicrobial stewardship principles. The single-dose azithromycin regimen offers practical advantages for travelers while maintaining efficacy 1.