What is the recommended treatment for typhoid fever?

Recommended Treatment for Typhoid Fever

The first-line treatment for typhoid fever is azithromycin 500 mg once daily for 7 days due to its superior efficacy compared to fluoroquinolones, lower risk of clinical failure, shorter hospital stays, and lower risk of relapse compared to ceftriaxone. 1

First-Line Treatment Options

• Azithromycin is recommended at 20 mg/kg/day (maximum 1g/day) for 7 days as the preferred first-line treatment, particularly in areas with high fluoroquinolone resistance 1
• For severe cases requiring hospitalization, intravenous ceftriaxone is recommended as initial therapy at 2g IV daily for adults and 50-80 mg/kg/day (maximum 2g/day) for children 2, 3
• Once clinical improvement occurs with IV therapy, transition to oral therapy (such as azithromycin) may be considered 2

Treatment Selection Based on Resistance Patterns

• Fluoroquinolones (including ciprofloxacin) should be avoided as empiric therapy for cases originating from South Asia due to high resistance rates (>70% of isolates) 1, 3, 4
• For fully susceptible strains, fluoroquinolones remain effective alternatives, but resistance testing should confirm sensitivity to nalidixic acid 2, 3
• In regions with high fluoroquinolone resistance, azithromycin or ceftriaxone should be used as first-line therapy 2, 1

Dosing Guidelines

Azithromycin

• Adults: 500 mg once daily for 7 days 1
• Children: 20 mg/kg/day (maximum 1g/day) for 7 days 2, 1

Ceftriaxone

• Adults: 1-2g IV/IM daily for 5-7 days (some guidelines recommend 14 days to reduce relapse risk) 2, 3
• Children: 50-80 mg/kg/day IV/IM (maximum 2g/day) for 5-7 days 2

Special Considerations

• Blood cultures should be obtained before starting antibiotics when possible, as they have the highest yield within the first week of symptom onset 2, 3
• Fever typically resolves within 4-5 days of appropriate therapy, with azithromycin showing faster fever clearance (mean 5.8 days) compared to ceftriaxone (7.1 days) and ciprofloxacin (8.2 days) 1, 5
• Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients, particularly if illness duration exceeds 2 weeks 3

Common Pitfalls to Avoid

• Relying solely on ciprofloxacin disc testing for antibiotic sensitivity is unreliable; the organism should also be sensitive to nalidixic acid to be considered truly sensitive to fluoroquinolones 3
• Using fluoroquinolones empirically for cases originating from South Asia despite high resistance rates 1, 4
• Inadequate treatment duration, which can increase relapse risk 3
• Assuming previous typhoid vaccination provides complete protection; vaccines offer incomplete protection and do not protect against paratyphoid 3

Treatment Algorithm

1. For uncomplicated typhoid fever:

   • First choice: Azithromycin 500 mg once daily for 7 days (adults) or 20 mg/kg/day for 7 days (children) 1
   • Alternative: Cefixime 16 mg/kg/day for 14 days 5

2. For severe cases requiring hospitalization:

   • Initial therapy: Ceftriaxone 2g IV daily (adults) or 50-80 mg/kg/day IV (children) 2, 3
   • Once improved: Transition to oral azithromycin to complete treatment course 2

3. For fully susceptible strains (confirmed by testing):

   • Fluoroquinolones may be used if sensitivity to both ciprofloxacin and nalidixic acid is confirmed 2, 3