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

Treatment Algorithm Based on Resistance Patterns

First-line Treatment Options:

1. For fully sensitive Salmonella typhi:

   • Fluoroquinolones (ciprofloxacin, ofloxacin) 1
   • Alternative if fluoroquinolones unavailable: chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole 1

2. For multidrug-resistant strains:

   • Fluoroquinolones or cefixime 1
   • Alternative: azithromycin 1

3. For quinolone-resistant strains:

   • Azithromycin or ceftriaxone 1
   • Alternative: cefixime 1

Dosing Recommendations:

• Azithromycin: 10 mg/kg/day (maximum 500 mg/day) for 7 days 2
• Ceftriaxone: 75 mg/kg/day in two divided doses (maximum 2-2.5 g/day) 3, 2
• Ciprofloxacin: As indicated for typhoid fever in FDA labeling 4

Evidence for Treatment Recommendations

Azithromycin vs. Fluoroquinolones

• Azithromycin shows lower risk of clinical failure (OR 0.48; 95% CI, 0.26-0.89) 1
• Shorter hospital stay with azithromycin (-1.04 days; 95% CI, -1.73 to -0.34 days) 1

Azithromycin vs. Ceftriaxone

• Azithromycin demonstrates lower risk of relapse (OR 0.09; 95% CI, 0.01-0.70) 1
• However, ceftriaxone may result in shorter time to defervescence (mean difference -0.52 days) 5

Ceftriaxone Efficacy

• Flexible-duration ceftriaxone therapy (until defervescence plus 5 additional days) shows good efficacy 3
• Mean defervescence time with ceftriaxone is approximately 4-5.4 days 6, 3

Special Considerations

Duration of Treatment

• Azithromycin: 7 days 2
• Ceftriaxone: Until defervescence plus 5 additional days 3
• Fluoroquinolones: As directed by susceptibility testing and clinical response

Resistance Patterns

• Increasing resistance to fluoroquinolones, particularly among travelers to South and Southeast Asia 1
• Resistance to nalidixic acid (a marker for decreased susceptibility to ciprofloxacin) increased from 19% in 1999 to 59% in 2008 1
• Emergence of extensively drug-resistant strains in some regions 5

Common Pitfalls to Avoid

1. Delaying antimicrobial therapy when infection is strongly suspected in critically ill patients 7
2. Failing to obtain cultures before initiating antimicrobial therapy 7
3. Overlooking resistance patterns in the patient's region of travel or exposure 1
4. Using ciprofloxacin in areas with known ciprofloxacin-resistant strains 1
5. Focusing solely on fever reduction rather than treating the underlying infection 7
6. Inadequate duration of therapy leading to treatment failure or relapse 3

Diagnostic Approach

• Blood cultures have the highest yield within the first week of symptom onset 7
• For travelers returning from endemic areas, consider typhoid fever in the differential diagnosis 1, 7
• Monitor temperature using accurate methods when making critical clinical decisions 7

Remember that resistance patterns vary by geographic location and are evolving over time. Treatment should be adjusted based on local antimicrobial susceptibility patterns and the patient's clinical response.