What are the treatment guidelines for typhoid fever?

Treatment Guidelines for Typhoid Fever

Azithromycin is the recommended first-line therapy for typhoid fever at a dosage of 20 mg/kg/day divided into two doses for 7-14 days, due to its lower risk of clinical failure, shorter hospital stay, and lower risk of relapse compared to other antibiotics. 1

First-Line Treatment Options

Azithromycin

• Dosage: 20 mg/kg/day divided into two doses for 7-14 days
• Benefits:
  • Excellent efficacy against multidrug-resistant and quinolone-resistant strains
  • Lower relapse rates compared to ceftriaxone 1
  • Safe for use in children and pregnant women 1
  • Effective for uncomplicated typhoid fever with clinical cure rates of 91-94% 2, 3

Ceftriaxone

• Dosage: 1-2 g IV once daily for 7-14 days
• Particularly useful for:
  • Severe infections
  • When oral therapy isn't possible 1
  • Safe during pregnancy 1
• Caution: Higher relapse rates compared to azithromycin 1, 4

Treatment Based on Resistance Patterns

Strain	Recommended Treatment	Alternative Options
Fully sensitive	Azithromycin	Fluoroquinolones, chloramphenicol, amoxicillin, TMP-SMX
Multidrug-resistant	Azithromycin or fluoroquinolones	Cefixime
Quinolone-resistant	Azithromycin or ceftriaxone	Cefixime

Treatment Duration

• Uncomplicated typhoid fever: 7-14 days of therapy 1
• Immunocompromised patients:
  • CD4+ counts >200 cells/μL: 7-14 days
  • CD4+ count <200 cells/μL: 2-6 weeks 1
• Continue treatment for the full course even if symptoms resolve earlier 1
• Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy 1

Special Populations

Children

• Azithromycin is preferred (20 mg/kg/day) 1, 2
• Avoid fluoroquinolones when possible due to concerns about joint/cartilage toxicity 1
• Studies show 5-day courses of azithromycin can be effective in children with uncomplicated typhoid fever 2

Pregnant Women

• Azithromycin is preferred due to its safety profile 1
• Ceftriaxone is also considered safe during pregnancy 1

Management of Treatment Failure

For patients failing to respond to initial therapy:

1. Reassess antimicrobial susceptibility
2. Consider switching to an alternative agent based on susceptibility testing
3. Consider extending duration of therapy
4. Evaluate for complications such as intestinal perforation or abscess formation 1

Monitoring Response

• Monitor fever clearance time (typically 3-5 days with effective therapy)
• Ensure clinical improvement within 48-72 hours of initiating appropriate therapy 1
• Follow-up blood cultures are not routinely needed if clinical response is adequate 1
• Consider follow-up cultures for patients who fail to respond clinically to appropriate therapy 1

Important Considerations

Antimicrobial Resistance

• Increasing resistance to fluoroquinolones is a significant concern, particularly in South and Southeast Asia 1
• Nalidixic acid resistance (a marker for decreased ciprofloxacin susceptibility) increased from 19% in 1999 to 59% in 2008 1
• 96% of S. Typhi isolates in some regions are resistant to nalidixic acid, and 58% are multidrug resistant 5

Cost Considerations

• Azithromycin is approximately one-third the cost of other treatments in some regions, making it more accessible 5

Treatment Efficacy Comparison

• Meta-analysis shows azithromycin is marginally better than older fluoroquinolones in reducing clinical failure (RR 0.46,95% CI 0.25-0.82) 6
• Azithromycin significantly reduces the chance of relapse compared to ceftriaxone (RR 0.1,95% CI 0.01-0.76) 6

Prevention

• Typhoid vaccination for travelers to endemic areas
• Proper hand hygiene and food safety practices
• Avoiding high-risk foods and beverages in endemic areas 1