Treatment of Typhoid Fever
Azithromycin is the recommended first-line treatment for typhoid fever at a dose of 20 mg/kg/day for 7 days, particularly in areas with high rates of nalidixic acid resistance and multidrug resistance. 1
Treatment Algorithm Based on Resistance Patterns
First-Line Treatment Options:
Fully sensitive S. typhi:
- Azithromycin 20 mg/kg/day for 7 days (preferred)
- Alternative: Fluoroquinolones, chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole
Multidrug-resistant S. typhi:
- Fluoroquinolones (if local resistance patterns permit) or cefixime
- Alternative: Azithromycin
Quinolone-resistant S. typhi:
- Azithromycin 20 mg/kg/day for 7 days
- Alternative: Ceftriaxone or cefixime
Special Patient Populations
Children and Pregnant Women:
- Preferred treatment: Azithromycin due to its superior safety profile 1
- Avoid: Fluoroquinolones (including ciprofloxacin) due to potential adverse effects on developing cartilage
Adults:
- Azithromycin 20 mg/kg/day for 7 days
- Alternative: Ciprofloxacin (except in South Asia due to high resistance) 2
- Ceftriaxone for severe cases or when oral therapy isn't possible
Efficacy Considerations
Azithromycin demonstrates several advantages:
- Faster fever clearance times (<4 days)
- Higher clinical cure rates compared to fluoroquinolones
- Lower relapse rates (<3%) compared to ceftriaxone (<8%) 1
- Superior to ofloxacin with lower risk of clinical failure (OR 0.48; 95% CI 0.26-0.89) 1
- Shorter hospital stays by approximately 1 day compared to ofloxacin 1
Resistance Patterns to Consider
- 96% of S. typhi isolates show resistance to nalidixic acid
- 58% are multidrug-resistant 1, 3
- Ciprofloxacin resistance is common in South Asia, particularly Pakistan 2
- Treatment should be guided by local resistance patterns
Treatment Response and Follow-up
- Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy 1
- Complete symptom resolution usually occurs within 4-7 days
- Follow-up testing is not routinely recommended after symptom resolution except for food handlers, healthcare workers, or childcare providers
Important Caveats
Regional resistance patterns: Always consider local resistance patterns when selecting therapy. Ciprofloxacin should be avoided in South Asia due to high resistance rates.
Treatment failures: In cases of treatment failure with ceftriaxone, switching to ciprofloxacin has shown rapid improvement (within 48 hours) in patients where local resistance patterns permit 4.
Cost considerations: Gatifloxacin (a newer fluoroquinolone) costs approximately one-third of azithromycin in some regions and shows similar efficacy, which may be relevant in resource-limited settings 3.
Duration of therapy: A 7-day course of azithromycin is standard, while shorter 5-day courses of ceftriaxone have shown efficacy comparable to longer courses of other antibiotics 5.
By following this evidence-based approach to treating typhoid fever, focusing on azithromycin as first-line therapy while considering local resistance patterns, clinicians can optimize patient outcomes and reduce the risk of treatment failure.