Recommended Treatment for Typhoid Fever
Azithromycin 500 mg once daily for 7 days is the recommended first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, due to its superior efficacy, lower risk of clinical failure, and shorter hospital stays. 1
First-Line Treatment Options
- Azithromycin 500 mg once daily on day 1, followed by 500 mg once daily for 6 more days (total 7 days) is the preferred treatment for adults with typhoid fever 2
- Azithromycin demonstrates superior efficacy compared to fluoroquinolones for treating typhoid fever, with a lower risk of clinical failure (OR 0.48) and shorter hospital stays 2
- Azithromycin has a lower risk of relapse (OR 0.09) compared to ceftriaxone and is particularly effective against quinolone-resistant strains 1, 2
Alternative Treatment Options Based on Resistance Patterns
- For fully susceptible S. typhi strains, fluoroquinolones (ofloxacin or ciprofloxacin) or alternatives such as chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole can be considered 1
- For severe cases, intravenous ceftriaxone may be used initially, with transition to oral therapy when clinically improved 3
- Ciprofloxacin is FDA-approved for typhoid fever but should not be used empirically for cases originating from South Asia due to high resistance rates 4, 5
Special Considerations
- For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started after collection of blood, stool, and urine cultures 3
- Expected fever clearance is within 4-5 days of appropriate therapy 1
- Treatment should be guided by local resistance patterns, as resistance to fluoroquinolones is common, particularly among travelers to South and Southeast Asia 1, 5
- The addition of steroids may be helpful in severe cases of typhoid fever 3
Pediatric Dosing
- For children with typhoid fever, azithromycin at 10 mg/kg/day (maximum 500 mg/day) for 7 days has shown high cure rates (91%) 6
- Alternatively, ceftriaxone at 75 mg/kg/day (maximum 2.5 g/day) can be used for children 6
Monitoring and Follow-up
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1
- Watch for potential drug interactions with azithromycin, particularly with agents metabolized by cytochrome P450 enzyme system 2
- Common adverse effects of azithromycin include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 2
Treatment Failure Management
- If poor response to azithromycin occurs, consider confirming antimicrobial susceptibility testing if available 2
- Alternative options include switching to a third-generation cephalosporin (e.g., ceftriaxone) or combination therapy with cefixime 2
- Ceftriaxone has shown efficacy in bacteremic typhoid fever with a mean defervescence period of 4 days 7
Prevention
- Typhoid vaccination provides incomplete protection and does not protect against paratyphoid 1, 3
- Careful selection of food and drink is essential, as typhoid vaccines are not 100% effective 8