What is the most appropriate empiric antibiotic for an otherwise healthy adult presenting with acute diarrhoea and fever?

Best Antibiotic for Diarrhea with Fever

For an otherwise healthy adult with acute diarrhea and fever, azithromycin is the preferred first-line empiric antibiotic, with ciprofloxacin reserved as second-line only in areas with documented low fluoroquinolone resistance. 1, 2

When to Use Empiric Antibiotics

Empiric antibiotics are indicated in specific clinical scenarios, not for all cases of diarrhea with fever:

• Fever documented in a medical setting, abdominal pain, bloody diarrhea, and bacillary dysentery (frequent scant bloody stools, fever, abdominal cramps, tenesmus) presumptively due to Shigella 1
• Recent international travel with temperature ≥38.5°C and/or signs of sepsis 1
• Clinical features of sepsis with suspected enteric fever (after obtaining blood, stool, and urine cultures) 1
• Immunocompromised patients with severe illness and bloody diarrhea 1

Most immunocompetent adults with acute watery diarrhea and fever do NOT require empiric antibiotics, even with fever, unless the above criteria are met. 1

First-Line Antibiotic Choice

Azithromycin is superior to fluoroquinolones because fluoroquinolone-resistant Campylobacter now exceeds 90% in many regions, including Thailand and India. 2, 3

Azithromycin Dosing:

• Single 1-gram dose for moderate to severe cases 2, 3
• OR 500 mg once daily for 3 days 2, 4, 3

Azithromycin is effective against the most common bacterial pathogens causing febrile diarrhea: Campylobacter, Shigella, Salmonella, and enterotoxigenic E. coli. 2, 3

Second-Line Antibiotic Choice

Ciprofloxacin should only be used when:

• Local susceptibility patterns are favorable (fluoroquinolone resistance <10%) 1, 2
• Azithromycin is contraindicated or unavailable 2
• The patient has not traveled to Southeast Asia or India 2, 3

Ciprofloxacin Dosing:

• 500 mg orally every 12 hours for 5-7 days 5
• OR 750 mg single dose for moderate to severe cases 2

The 2017 IDSA guidelines state that empiric therapy should be "either a fluoroquinolone such as ciprofloxacin, or azithromycin, depending on the local susceptibility patterns and travel history," but the weight of current evidence strongly favors azithromycin first. 1

Treatment Duration

• Standard duration: 3-5 days for most bacterial diarrhea 4, 3
• Single-dose therapy is acceptable for azithromycin (1 gram) or ciprofloxacin (750 mg) in moderate to severe travelers' diarrhea 2, 3
• Typhoid fever requires 10 days of ciprofloxacin 500 mg every 12 hours 5

Critical Contraindications

NEVER give antibiotics for suspected or confirmed STEC (Shiga toxin-producing E. coli) O157:H7 or other Shiga toxin 2-producing strains, as this significantly increases the risk of hemolytic uremic syndrome. 1, 2

Do not treat:

• Asymptomatic contacts of patients with diarrhea 1
• Uncomplicated watery diarrhea without fever, blood, or recent international travel 1
• Non-typhoidal Salmonella in healthy adults (unless severe illness, age <6 months or >50 years, or immunocompromised) 2

Common Pitfalls to Avoid

• Do not start antibiotics for bloody diarrhea until STEC has been ruled out with stool culture and Shiga toxin testing 2
• Do not use fluoroquinolones empirically without reviewing local resistance data and travel history, as resistance exceeds 90% in many regions 2, 3
• Do not neglect rehydration therapy, which remains the cornerstone of all diarrhea management regardless of antibiotic use 1, 2
• Reassess within 48-72 hours if no clinical improvement for antibiotic resistance, inadequate rehydration, or non-infectious causes 2, 4

Special Populations

• Infants <3 months: Use third-generation cephalosporin (ceftriaxone 50 mg/kg/day), not azithromycin or ciprofloxacin 1, 2
• Pregnant women: Azithromycin is preferred; avoid fluoroquinolones 1
• Immunocompromised patients: Azithromycin 500 mg daily for 3-7 days depending on severity 2, 4