What is the recommended management for typhoid fever?

Management of Typhoid Fever

For typhoid fever, the recommended first-line treatment is azithromycin 500 mg once daily for 7 days, particularly in areas with high fluoroquinolone resistance. 1

First-Line Treatment Options

• Azithromycin: 500 mg once daily on day 1, followed by 500 mg once daily for 6 more days (total 7 days) for adults with typhoid fever 1

  • Superior efficacy compared to fluoroquinolones with lower risk of clinical failure (OR 0.48) and shorter hospital stays 1
  • Lower risk of relapse (OR 0.09) compared to ceftriaxone 1
  • Particularly effective against quinolone-resistant strains 1, 2

• Fluoroquinolones (if local susceptibility is confirmed):

  • Ciprofloxacin 500 mg twice daily for 7-10 days 3
  • Not recommended for cases originating from South Asia due to high resistance rates 4
  • Resistance to nalidixic acid is a marker for decreased susceptibility to ciprofloxacin 5

• Third-generation cephalosporins:

  • Ceftriaxone (IV): Recommended for severe cases or when oral therapy is not possible 5, 6
  • Typically administered for 7-14 days depending on severity 3

Treatment Algorithm Based on Resistance Patterns

1. For fully susceptible S. typhi:

   • Fluoroquinolones (ofloxacin or ciprofloxacin) 2
   • Alternatives: chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole 2

2. For multidrug-resistant strains:

   • Fluoroquinolone (if susceptible) or cefixime 2
   • Alternative: azithromycin 2

3. For quinolone-resistant strains:

   • Azithromycin as preferred treatment 2, 1
   • Alternative: ceftriaxone or cefixime 2

Special Considerations

• Severe cases: Consider IV ceftriaxone initially, with transition to oral therapy when clinically improved 5, 6
• Complications: For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started after collection of blood, stool, and urine cultures 5
• Steroids: May be beneficial in severe cases of typhoid fever 5
• Treatment duration: 7-14 days is typical, with longer courses for severe infections 3

Monitoring and Follow-up

• Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 7, 6
• Watch for potential drug interactions with azithromycin, particularly with agents metabolized by cytochrome P450 enzyme system 1
• Common adverse effects of azithromycin include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1

Treatment Failure Management

• If poor response to initial therapy, consider:
  • Confirming antimicrobial susceptibility testing if available 1
  • Switching to a third-generation cephalosporin (e.g., ceftriaxone) 1
  • Combination therapy with cefixime may be considered 1

Prevention

• Typhoid vaccination provides incomplete protection and does not protect against paratyphoid 5
• Water, sanitation, and hygiene measures are cornerstones of prevention 4

Pitfalls to Avoid

• Do not use ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 4
• Ciprofloxacin disc testing is unreliable; the organism should also be sensitive to nalidixic acid to be considered sensitive to fluoroquinolones 5
• Do not delay treatment when there is strong clinical suspicion, as early treatment results in better outcomes 5
• Recognize that increasing resistance to fluoroquinolones has been observed, particularly among travelers to South and Southeast Asia 2