Recommended Treatment for Typhoid Fever
The recommended first-line treatment for typhoid fever is azithromycin at a dosage of 20 mg/kg/day for 7 days, especially in areas with high resistance to fluoroquinolones and for vulnerable populations such as children and pregnant women. 1
Treatment Options Based on Antibiotic Sensitivity
Treatment should be guided by local resistance patterns and strain sensitivity:
For Different Strains of Salmonella Typhi:
| 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 Considerations:
- Azithromycin achieves faster fever clearance times (<4 days) and higher clinical cure rates compared to fluoroquinolones, with relapse rates <3% 1
- Ceftriaxone is an effective alternative, typically administered at 75 mg/kg/day (maximum 2g/day) intravenously in two divided doses 2, 3
- Fluoroquinolones like ciprofloxacin should be avoided in south Asia due to high resistance rates (96% of Salmonella Typhi isolates show resistance to nalidixic acid and 58% are multidrug-resistant) 1, 4
Special Population Considerations
- Children: Azithromycin is preferred; alternatively, ceftriaxone at 75 mg/kg/day can be used 2
- Pregnant women: Avoid fluoroquinolones; use azithromycin, ampicillin, cefotaxime, or ceftriaxone 1
- Immunocompromised patients: Consider longer duration of therapy with ceftriaxone or azithromycin 1
- HIV-infected persons with Salmonella septicemia: Require long-term therapy to prevent recurrence 1
Treatment Duration and Monitoring
- Standard treatment duration: 7 days for azithromycin 1, 4
- For ceftriaxone: A flexible-duration approach until defervescence plus 5 additional days has shown good results 2
- Consider changing antibiotics if no improvement is seen within 2 days of starting treatment 1
- Monitor for defervescence, which typically occurs within 4-5 days of starting appropriate therapy 2, 3
Prevention Strategies
- Typhoid vaccination is recommended for travelers to endemic areas 1
- Proper hand hygiene is essential, especially after using the toilet and before food preparation 1
- Careful selection of food and drink in endemic areas, as vaccines are not 100% effective 5
Common Pitfalls and Caveats
- Avoid antimotility agents as they may worsen outcomes in enteric infections 1
- Don't rely solely on clinical presentation for diagnosis; blood cultures are essential for confirmed diagnosis 1
- Beware of altered symptom presentation in patients who have previously used antimicrobials 4
- Don't underestimate the importance of follow-up in high-risk individuals such as food handlers, healthcare workers, or childcare providers 1
- Remember that resistance patterns vary geographically; treatment should be guided by local resistance patterns 1, 4
Complications Management
- Surgical intervention is often necessary for vascular infections and endocarditis 1
- Life-threatening complications can arise in the second week of untreated illness 4
- Household contacts should be evaluated for asymptomatic carriage 1
The evidence strongly supports azithromycin as the current first-line treatment for typhoid fever due to its efficacy, safety profile, and effectiveness against resistant strains, with ceftriaxone as an excellent alternative, particularly for severe cases requiring parenteral therapy.