What is the recommended treatment for typhoid fever?

Typhoid Fever Treatment Guidelines

Ceftriaxone is the first-line treatment for typhoid fever due to its high efficacy and lower resistance rates, particularly in regions with high fluoroquinolone resistance. 1

First-Line Treatment Options

Ceftriaxone

• Recommended as first-line empiric treatment by the World Health Organization 1
• Dosage: 50-80 mg/kg/day for 7-10 days 1
• Advantages:
  • High efficacy with reliable sensitivity patterns globally
  • Suitable for severe infections or when oral therapy isn't possible
  • Safe alternative during pregnancy 1

Azithromycin

• Excellent alternative first-line option 1
• Advantages:
  • Lower risk of clinical failure compared to fluoroquinolones
  • Lower relapse rates (<3%) compared to ceftriaxone (<8%) 1
  • Preferred for children and pregnant women due to safety profile 1

Treatment Algorithm Based on Resistance Patterns

1. For fully sensitive strains:

   • Azithromycin as first choice
   • Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole 1

2. For multidrug-resistant strains:

   • Fluoroquinolones (if susceptible) or cefixime
   • Alternative: Azithromycin 1

3. For quinolone-resistant strains:

   • Azithromycin or ceftriaxone
   • Alternative: Cefixime 1

Important Treatment Considerations

• Treatment duration: Continue for 14 days to reduce relapse risk 1
• Expected response: Clinical improvement typically occurs within 48-72 hours; fever clearance time is usually <4 days with appropriate treatment 1
• Monitoring: Closely observe for clinical response, particularly when using cefixime which has higher failure rates (4-37.6%) compared to other options 1

Antimicrobial Resistance Concerns

• More than 70% of Salmonella typhi isolates imported to the UK are resistant to fluoroquinolones 1
• Ciprofloxacin is FDA-approved for typhoid fever but should be used with caution due to increasing resistance, particularly in South and Southeast Asia 2, 1
• Using ciprofloxacin discs alone to determine Salmonella typhi sensitivity is unreliable; the organism should also be sensitive to nalidixic acid on disc testing 1

Special Populations

• Pregnant women: Ceftriaxone is considered safe and particularly useful for severe infections 1
• Children: Azithromycin is preferred due to its safety profile; avoid fluoroquinolones when possible 1

Comparative Efficacy

• A Cochrane review found ceftriaxone to be an effective treatment for adults and children with enteric fever, with few adverse effects 3
• A randomized controlled trial comparing azithromycin and ceftriaxone in children showed high cure rates for both: 91% for azithromycin and 97% for ceftriaxone 4
• Gatifloxacin and azithromycin showed similar efficacy in a randomized controlled trial, with median fever clearance time of 106 hours in both treatment arms 5

Prevention

• Typhoid vaccination is recommended for travelers to endemic areas
• Proper hand hygiene and food safety practices are essential
• Avoid high-risk foods and beverages in endemic areas 1

Common Pitfalls to Avoid

• Using fluoroquinolones empirically without considering local resistance patterns
• Relying on the serological Widal test for diagnosis due to its poor sensitivity and specificity 1
• Using antimotility agents in patients with high fever or blood in stool 1
• Stopping treatment early, which can lead to relapse 1
• Using ciprofloxacin in areas with known high resistance rates