What is the recommended single-dose antibiotic for an otherwise healthy adult with acute, uncomplicated diarrhea?

Single-Dose Antibiotic for Acute Diarrhea

Azithromycin 1000 mg as a single oral dose is the preferred antibiotic for single-dose treatment of acute diarrhea in otherwise healthy adults. 1

Primary Recommendation: Azithromycin

For moderate to severe acute diarrhea requiring antibiotic therapy, azithromycin 1000 mg orally as a single dose is the first-line choice. 1, 2 This recommendation is based on:

• Strong evidence supporting single-dose efficacy with equivalent outcomes to 3-day regimens 1
• Superior coverage for fluoroquinolone-resistant Campylobacter, which is increasingly prevalent globally (>85-90% resistance in Southeast Asia) 1, 3
• Effectiveness for both watery and dysenteric (bloody/febrile) diarrhea 1, 2
• Better adherence compared to multi-day regimens 2

Alternative Single-Dose Options

If azithromycin is unavailable or contraindicated, fluoroquinolones can be used as second-line agents in areas with low resistance: 1, 2

• Ciprofloxacin 750 mg orally as a single dose 1, 4
• Levofloxacin 500 mg orally as a single dose 1, 5

Critical caveat: Fluoroquinolones should NOT be used for dysentery or febrile diarrhea where Campylobacter is suspected, particularly in travelers to Southeast Asia, India, or sub-Saharan Africa, due to high resistance rates. 1, 2

When Single-Dose Antibiotics Are Appropriate

Single-dose antibiotic regimens are indicated for: 1

• Moderate to severe travelers' diarrhea causing incapacitation or inability to carry out planned activities 1
• Dysentery (bloody stools with fever >38.5°C) 1
• Severe watery diarrhea with significant impact on function 1

When Antibiotics Should NOT Be Used

Do not use antibiotics for: 1, 2

• Mild, self-limited watery diarrhea without fever or blood 2, 3
• Suspected STEC O157 or Shiga toxin-producing E. coli, as antibiotics increase risk of hemolytic uremic syndrome 6, 3
• Most cases of acute diarrhea in otherwise healthy adults, where loperamide alone provides adequate symptomatic relief 1

Combination Therapy Consideration

Loperamide can be added to antibiotic therapy for faster symptom relief: 1, 3

• Initial dose: 4 mg orally, then 2 mg after each loose stool (maximum 16 mg/24 hours) 1
• Do not use loperamide if bloody diarrhea or fever is present, as this increases risk of toxic megacolon 1, 3

Geographic and Resistance Considerations

Azithromycin should be the default choice in Southeast Asia regardless of severity due to extremely high fluoroquinolone resistance rates. 1, 2, 3 In other regions, fluoroquinolones remain acceptable alternatives for non-dysenteric diarrhea if local resistance patterns are favorable. 1, 2

Common Pitfalls to Avoid

• Do not use ciprofloxacin for dysentery or febrile diarrhea where Campylobacter is likely, as treatment failures are common with resistant strains 1, 7
• Avoid aluminum or magnesium-containing antacids with azithromycin, as they reduce absorption 2
• Do not continue loperamide if symptoms worsen, fever develops, or blood appears in stool 3
• Nausea occurs more frequently with azithromycin (8% vs 1% with levofloxacin) in the first 30 minutes after dosing, but is self-limited and does not require treatment 8

When to Seek Medical Intervention

Medical evaluation is required if: 1

• No improvement after 24-48 hours of treatment 1
• Development of high fever (>38.5°C), bloody stools, or signs of dehydration 1
• Patient is elderly (>75 years), immunocompromised, or has significant comorbidities 1, 3