Treatment of Typhoid Fever
Ceftriaxone is the recommended first-line treatment for typhoid fever due to its high efficacy and lower resistance rates, with azithromycin as a suitable alternative, particularly in regions with high fluoroquinolone resistance. 1
First-line Treatment Options
Ceftriaxone
- Dosage: 50-80 mg/kg/day for 7-10 days 1
- Advantages:
- High efficacy against Salmonella typhi
- Low resistance rates globally
- Suitable for severe infections or when oral therapy isn't possible
- Safe alternative during pregnancy 1
- All isolates reported to the UK Health Protection Agency are sensitive to ceftriaxone 1
Azithromycin
- Preferred alternative treatment option
- Lower risk of clinical failure compared to fluoroquinolones 1
- Lower relapse rates (<3%) compared to ceftriaxone (<8%) 1
- Especially suitable for:
- Children and pregnant women due to its safety profile
- Regions with high fluoroquinolone resistance 1
Treatment Selection Based on Resistance Patterns
| Strain | Recommended Treatment | Alternative Options |
|---|---|---|
| Fully sensitive | Azithromycin | Fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole |
| Multidrug-resistant | Fluoroquinolones or cefixime | Azithromycin |
| Quinolone-resistant | Azithromycin or ceftriaxone | Cefixime |
Important Clinical Considerations
- Treatment duration: Continue treatment for 14 days to reduce relapse risk 1
- Expected response:
- Fever clearance typically occurs within 4 days of appropriate treatment
- Clinical improvement usually within 48-72 hours 1
- Monitoring: Closely observe patients for clinical response, particularly when using medications with higher failure rates (e.g., cefixime) 1
Fluoroquinolone Considerations
- Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi 2
- However, its use is limited by high resistance rates:
- If susceptibility is confirmed, ciprofloxacin can be used at 15 mg/kg twice daily (maximum 500 mg twice daily) for 7-10 days 1
Cautions and Pitfalls
- Resistance testing: Using ciprofloxacin discs alone to determine Salmonella typhi sensitivity is unreliable; the organism should also be sensitive to nalidixic acid on disc testing 1
- Diagnostic limitations: The serological Widal test lacks sensitivity and specificity and is not recommended for diagnosis 1
- Avoid antimotility agents such as loperamide in patients with high fever or blood in stool 1
- Cefixime caution: Has reported treatment failure rates of 4-37.6%, making it less reliable than other options 1
Prevention Recommendations
- Typhoid vaccination for travelers to endemic areas
- Proper hand hygiene and food safety practices
- Avoiding high-risk foods and beverages in endemic areas 1
- Asymptomatic carriers in healthcare or food service should be treated according to public health guidance 1
The emergence of extensively drug-resistant strains of typhoid fever, particularly in South Asia, highlights the importance of appropriate antibiotic selection based on local resistance patterns and susceptibility testing when available.