What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin is the recommended first-line treatment for uncomplicated typhoid fever, with a dosage of 20 mg/kg/day for 7 days, due to its superior efficacy, safety profile, and effectiveness against resistant strains. 1

Treatment Algorithm Based on Resistance Patterns

First-line Treatment Options:

• Uncomplicated typhoid fever:
  • Azithromycin: 20 mg/kg/day for 7 days (preferred option)
    • Achieves faster fever clearance (<4 days)
    • Clinical cure rates higher than other options
    • Low relapse rates (<3%)
    • Preferred for children and pregnant women

Treatment Based on Resistance Pattern:

1. Fully sensitive strains:

   • Azithromycin (preferred)
   • Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole

2. Multidrug-resistant strains:

   • Fluoroquinolones (e.g., ciprofloxacin) or cefixime
   • Alternative: Azithromycin

3. Quinolone-resistant strains:

   • Azithromycin or ceftriaxone
   • Alternative: Cefixime 1

Specific Antibiotic Regimens

Azithromycin:

• Dosage: 20 mg/kg/day once daily for 7 days
• Advantages:
  • Effective against multidrug-resistant and nalidixic acid-resistant strains
  • Safe for children and pregnant women
  • Once-daily dosing improves compliance
  • Lower relapse rates compared to ceftriaxone 1, 2

Ceftriaxone:

• Dosage: 50-75 mg/kg/day IV (maximum 2-2.5g/day) in 1-2 divided doses
• Duration: Until defervescence plus 5 additional days
• Advantages:
  • Effective for severe cases or when oral therapy isn't possible
  • Mean defervescence time: approximately 4-5 days 3
• Disadvantages:
  • Requires parenteral administration
  • Higher cost than oral options 4, 3

Ciprofloxacin:

• Indication: FDA-approved for typhoid fever caused by Salmonella typhi
• Note: Not recommended as first-line due to increasing resistance
• Caution: Should be avoided in children and pregnant women when possible 1, 5

Special Populations

Children:

• Preferred treatment: Azithromycin 20 mg/kg/day for 7 days
• Alternative: Ceftriaxone 75 mg/kg/day (maximum 2.5 g/day) 2
• Caution: Fluoroquinolones should be avoided when possible due to potential joint/cartilage toxicity 1

Pregnant Women:

• Preferred treatment: Azithromycin
• Alternatives: Third-generation cephalosporins or ampicillin
• Avoid: Fluoroquinolones 1

Severe or Complicated Cases:

• Initial therapy: Ceftriaxone IV until clinical improvement
• Follow-up: Switch to oral therapy once clinically improved
• Duration: Typically 10-14 days total therapy 1

Monitoring and Follow-up

• Expect clinical improvement within 48-72 hours of starting appropriate therapy
• Consider changing antibiotic regimen if no improvement is seen within 2 days
• Symptoms typically resolve within 4-7 days with appropriate treatment 1

Important Clinical Considerations

• Local resistance patterns should guide empiric therapy choices, with 96% of Salmonella Typhi isolates showing resistance to nalidixic acid and 58% being multidrug-resistant
• Fluoroquinolone resistance is increasing globally, limiting their effectiveness
• Proper hand hygiene is essential to prevent transmission, especially after using the toilet and before food preparation 1

Pitfalls to Avoid

• Failing to consider local resistance patterns when selecting empiric therapy
• Using fluoroquinolones as first-line in children or pregnant women
• Stopping antibiotics prematurely when symptoms improve
• Not considering typhoid fever in returning travelers with fever from endemic regions
• Inadequate follow-up for food handlers, healthcare workers, or childcare providers who may require clearance testing 1