What is the recommended management for typhoid fever?

Management 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 high efficacy and safety profile, particularly in the context of increasing antimicrobial resistance. 1

Antibiotic Selection Based on Resistance Patterns

Treatment should be guided by local resistance patterns and strain susceptibility:

• Fully sensitive strains:

  • First choice: Azithromycin 20 mg/kg/day for 7 days
  • Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole 1

• Multidrug-resistant strains:

  • First choice: Fluoroquinolones or cefixime
  • Alternative: Azithromycin 1

• Quinolone-resistant strains:

  • First choice: Azithromycin or ceftriaxone
  • Alternative: Cefixime 1

Dosing Regimens

Adults:

• Ciprofloxacin: 500 mg orally twice daily for 10 days 2
• Azithromycin: 20 mg/kg/day (maximum 1000 mg/day) for 7 days 1

Children:

• Azithromycin: 20 mg/kg/day for 7 days (preferred due to safety profile) 1
• Ceftriaxone: 75 mg/kg/day (maximum 2.5 g/day) for 7 days 3

Treatment Efficacy and Monitoring

• Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy 1
• Consider changing antibiotic regimen if no improvement is seen within 2 days 1
• Complete resolution of symptoms typically occurs within 4-7 days with appropriate treatment 1

Special Considerations

• Pregnant women: Azithromycin is preferred due to its safety profile; avoid fluoroquinolones 1
• Children: Azithromycin is preferred; avoid fluoroquinolones when possible due to potential joint toxicity 1
• Immunocompromised patients: Consider longer duration of therapy and may require alternative treatment options such as ceftriaxone 1

Treatment of Complications

• Most intestinal complications should be managed conservatively 4
• Severe cases may require surgical intervention for complications such as intestinal perforation
• For toxic delirious states, steroids may be beneficial 4

Clinical Evidence Supporting Recommendations

• Azithromycin achieves faster fever clearance times (<4 days) compared to other antibiotics 1
• Relapse rates with azithromycin are lower (<3%) compared to ceftriaxone (<8%) 1, 3
• In a meta-analysis, azithromycin showed better outcomes compared to older fluoroquinolones with a risk ratio of 0.46 for clinical failure 5
• A randomized controlled trial comparing gatifloxacin and azithromycin showed similar efficacy with median fever clearance time of 106 hours in both groups 6

Prevention

• Typhoid vaccination is recommended for travelers to endemic areas 7, 1
• Proper hand hygiene is essential, especially after using the toilet and before food preparation 1
• Food handlers, healthcare workers, and childcare providers who have had typhoid fever may require follow-up testing 1

Common Pitfalls to Avoid

• Failing to consider local resistance patterns when selecting antibiotics
• Using fluoroquinolones in children and pregnant women when safer alternatives are available
• Not changing therapy when clinical improvement is not seen within 48-72 hours
• Inadequate duration of treatment, which can lead to relapse
• Overlooking the need for supportive care alongside antibiotic therapy

The increasing prevalence of multidrug-resistant and quinolone-resistant strains necessitates careful antibiotic selection based on local resistance patterns and individual patient factors.