What is the recommended treatment for typhoid fever?

Typhoid Fever Treatment Guidelines

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

First-Line Treatment Options

Ceftriaxone

• Dosage: 50-80 mg/kg/day for 7-10 days (adults and children)
• Administration: Intravenous or intramuscular
• Benefits: High efficacy, suitable for severe infections or when oral therapy isn't possible
• All isolates reported to health agencies show sensitivity to ceftriaxone 1
• Fever clearance time typically <4 days with clinical improvement within 48-72 hours 1

Azithromycin

• Dosage: 20 mg/kg/day once daily for 7 days (maximum 1g/day)
• Administration: Oral
• Benefits: Lower risk of clinical failure compared to fluoroquinolones, lower relapse rates (<3% vs <8% for ceftriaxone) 1
• Particularly suitable for children and pregnant women due to safety profile 1
• Excellent efficacy against both fully sensitive and multidrug-resistant strains 1

Treatment Algorithm Based on Resistance Patterns

1. For fully sensitive strains:

   • First choice: Azithromycin
   • Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole

2. For multidrug-resistant strains:

   • First choice: Ceftriaxone
   • Alternatives: Azithromycin

3. For quinolone-resistant strains:

   • First choice: Azithromycin or ceftriaxone
   • Alternative: Cefixime

Important Clinical Considerations

• Treatment duration: Continue treatment for 14 days to reduce relapse risk 1
• Monitoring: Expect clinical improvement within 48-72 hours of starting appropriate therapy 1
• Resistance testing: Ciprofloxacin disc testing alone is unreliable; the organism should also be sensitive to nalidixic acid on disc testing to be considered sensitive to fluoroquinolones 1

Special Populations

• Pregnant women: Ceftriaxone is considered safe during pregnancy 1
• Children: Azithromycin is preferred due to its safety profile; avoid fluoroquinolones when possible 1

Common Pitfalls to Avoid

1. Using fluoroquinolones empirically: More than 70% of Salmonella typhi isolates are resistant to fluoroquinolones in many regions 1

2. Inadequate treatment duration: Stopping treatment early increases relapse risk 1

3. Using cefixime as first-line therapy: Has reported treatment failure rates of 4-37.6% 1

4. Relying on the Widal test for diagnosis: Lacks sensitivity and specificity 1

5. Using antimotility agents: Avoid in patients with high fever or blood in stool 1

Evidence of Comparative Efficacy

• A Cochrane review found ceftriaxone to be an effective treatment with few adverse effects, with possibly no difference in performance compared to azithromycin, fluoroquinolones, or chloramphenicol 2

• A randomized controlled trial comparing azithromycin (20 mg/kg/day) and ceftriaxone (75 mg/kg/day) in children found high cure rates in both groups (91% for azithromycin and 97% for ceftriaxone) 3

• A 5-day course of ceftriaxone has been shown to be a useful alternative to conventional 14-day chloramphenicol therapy 4

The increasing antimicrobial resistance threatens the effectiveness of single-agent treatments, making it essential to monitor patients closely for clinical response and adjust therapy based on susceptibility testing and clinical improvement 1, 5.