What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin is the recommended first-line treatment for typhoid fever due to its lower risk of clinical failure, shorter hospital stay, and lower risk of relapse compared to fluoroquinolones and ceftriaxone. 1

First-Line Treatment Options

The choice of antibiotic depends on susceptibility patterns and geographic considerations:

For fully sensitive Salmonella typhi:

• First choice: Azithromycin
• Alternatives: Fluoroquinolones (ciprofloxacin, ofloxacin), chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole 1, 2

For multidrug-resistant strains:

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

For quinolone-resistant strains:

• First choice: Azithromycin
• Alternative: Ceftriaxone 1

Specific Antibiotic Regimens

1. Azithromycin:

   • 1 gram orally on day 1, then 500 mg daily for 5 more days 3
   • Benefits: Lower risk of clinical failure (OR 0.48), shorter hospital stay (-1.04 days), and lower risk of relapse (OR 0.09) 1

2. Fluoroquinolones (when susceptible):

   • Ciprofloxacin: 500 mg orally twice daily for 7 days 2, 4
   • Ofloxacin: 400 mg orally twice daily for 14 days 5

3. Chloramphenicol:

   • For susceptible strains, administer at therapeutic levels for 8-10 days after the patient becomes afebrile to reduce relapse risk 6

Geographic Considerations

• Increasing resistance to fluoroquinolones is observed, particularly among travelers to South and Southeast Asia 1
• Resistance to nalidixic acid (a marker for decreased ciprofloxacin susceptibility) increased from 19% in 1999 to 59% in 2008 1
• In areas with known high resistance rates, avoid empiric ciprofloxacin therapy 1

Treatment Duration

• Continue treatment for 7-14 days depending on the antibiotic used
• For chloramphenicol, continue therapy for 8-10 days after the patient becomes afebrile to reduce relapse risk 6

Special Populations

• Children: Azithromycin is preferred due to safety concerns with fluoroquinolones 1
• Pregnant women: Azithromycin is preferred over fluoroquinolones 3

Treatment Pitfalls to Avoid

• Using ciprofloxacin in areas with known ciprofloxacin-resistant strains 1
• Failing to obtain cultures before initiating antimicrobial therapy
• Overlooking resistance patterns in the patient's region of travel or exposure 1
• Stopping treatment too early, which may increase relapse risk, especially with chloramphenicol 6
• Using combination therapy with paratyphoid A and B antigens, which increases the risk of vaccine reactions 7

Monitoring Response

• Monitor fever clearance time (typically 3-5 days with effective therapy) 4, 3
• Ensure clinical improvement within 48-72 hours of initiating appropriate therapy
• Consider treatment failure if fever persists beyond 5-7 days

In conclusion, azithromycin has emerged as the preferred first-line agent for typhoid fever due to its excellent efficacy profile, lower relapse rates, and effectiveness against resistant strains. Fluoroquinolones remain an option for fully susceptible strains, but increasing resistance limits their empiric use, particularly in South and Southeast Asia.