Treatment of Typhoid Fever
The recommended first-line treatment for typhoid fever is ceftriaxone (50-80 mg/kg/day for 7-10 days) due to its high efficacy and suitability for severe infections, especially in areas with fluoroquinolone resistance. 1
Antibiotic Selection Algorithm
First-line Options:
Ceftriaxone: 50-80 mg/kg/day IV for 7-10 days
- Preferred for severe infections or when oral therapy isn't possible
- Effective against multidrug-resistant strains
- May have longer time to defervescence compared to fluoroquinolones
Azithromycin: 20 mg/kg/day orally once daily for 7 days
- Excellent option for children and pregnant women
- Lower relapse rates (<3%) compared to ceftriaxone (<8%)
- Particularly useful in areas with fluoroquinolone resistance
Ciprofloxacin: 750 mg orally twice daily for 14 days
- FDA-approved for typhoid fever 2
- Not recommended for cases originating from South Asia due to high resistance rates
- Contraindicated in children and pregnant women when alternatives are available
Treatment Selection Based on Resistance Patterns
| Strain Type | First Choice | Alternative Options |
|---|---|---|
| Fully sensitive | Azithromycin | Fluoroquinolones, chloramphenicol, amoxicillin, TMP-SMX |
| Multidrug-resistant | Ceftriaxone | Azithromycin, fluoroquinolones (if susceptible) |
| Quinolone-resistant | Azithromycin or ceftriaxone | Cefixime |
Clinical Response Monitoring
- Fever typically clears within 4 days with appropriate treatment 1
- Clinical improvement should occur within 48-72 hours of starting therapy
- If no improvement after 72 hours, consider:
- Alternative diagnosis
- Antimicrobial resistance
- Development of complications
- Need for surgical intervention (in case of intestinal perforation)
Special Populations
Children
- Ceftriaxone is preferred first-line therapy
- Azithromycin is an excellent alternative due to safety profile
- Avoid fluoroquinolones when possible due to risk of arthropathy
Pregnant Women
- Azithromycin is preferred first-line therapy
- Ceftriaxone is a safe alternative
- Avoid fluoroquinolones
Severe Disease/Complications
- Parenteral ceftriaxone is indicated
- Consider longer duration of therapy (14 days)
- Monitor for complications including intestinal perforation, gastrointestinal bleeding, and encephalopathy
Common Pitfalls to Avoid
Using fluoroquinolones empirically: Fluoroquinolone resistance is widespread, particularly in South Asia. Ceftriaxone or azithromycin are safer empiric choices.
Inadequate treatment duration: Shorter courses may lead to relapse. Complete the full 7-10 day course even if symptoms resolve earlier.
Failure to monitor for complications: Typhoid can cause serious complications including intestinal perforation and neurological manifestations.
Ignoring resistance patterns: Treatment should be guided by local resistance patterns and adjusted based on susceptibility testing.
Overlooking carriers: Some patients become chronic carriers after treatment. Food handlers and healthcare workers should be monitored for carriage.
Evidence Comparison
The evidence regarding ceftriaxone versus fluoroquinolones shows mixed results. While older studies suggested fluoroquinolones might have faster fever clearance 3, increasing resistance has limited their utility. A 2022 Cochrane review concluded that ceftriaxone is an effective treatment with few adverse effects, though it noted limitations in the available evidence 4.
When comparing ceftriaxone to azithromycin, the evidence suggests that ceftriaxone may result in faster defervescence (by approximately 0.5 days) but potentially higher relapse rates 1, 5.
Given the emergence of extensively drug-resistant typhoid strains in Pakistan and widespread fluoroquinolone resistance in South Asia 6, ceftriaxone remains a reliable first-line option, with azithromycin as an excellent alternative, particularly for oral therapy.