Antibiotics for Typhoid Fever Treatment
Azithromycin is the recommended first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, due to its superior efficacy with lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones. 1
First-Line Treatment Options
- Azithromycin 500 mg once daily for 7 days for adults is recommended as first-line therapy, especially in areas with high fluoroquinolone resistance 1
- Azithromycin demonstrates a lower risk of relapse (OR 0.09) compared to ceftriaxone and is particularly effective against quinolone-resistant strains 1, 2
- For fully susceptible S. typhi, fluoroquinolones (ofloxacin or ciprofloxacin) remain effective options, with alternatives including chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole 3
Treatment Based on Resistance Patterns
- For fully sensitive Salmonella typhi: fluoroquinolones remain first-line, with azithromycin as an alternative 2
- For multidrug-resistant strains: fluoroquinolones or cefixime, with azithromycin as an alternative 2
- For quinolone-resistant strains: azithromycin or ceftriaxone is recommended as first-line therapy 2
- Ciprofloxacin should not be used empirically for cases originating from South Asia due to high resistance rates 1
Severe Cases and Special Considerations
- For severe cases requiring parenteral therapy: IV ceftriaxone initially (50-60 mg/kg/day in two divided doses), with transition to oral therapy when clinically improved 1, 4
- Ceftriaxone has demonstrated efficacy with a mean defervescence period of 4 days and can be successful with 5-8 days of therapy 4
- For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started after collection of blood, stool, and urine cultures 5
Treatment Duration and Monitoring
- Treatment should be continued for 10-14 days to reduce risk of relapse 2
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1
- Blood cultures have the highest yield within the first week of symptom onset 5
Complications and Prevention
- Complications of typhoid fever (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) occur in 10-15% of patients and are more likely if duration of illness exceeds 2 weeks 2
- Vaccination provides incomplete protection against typhoid fever and does not protect against paratyphoid 1, 5
Common Pitfalls to Avoid
- Avoid using ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 1
- Be aware that ciprofloxacin disc testing is unreliable; the organism should also be sensitive to nalidixic acid to be considered sensitive to fluoroquinolones 5
- Recognize that increasing resistance to fluoroquinolones has been observed, particularly among travelers to South and Southeast Asia 1
- Consider that azithromycin sensitivity testing is not readily available in many settings, though resistance remains relatively rare in many regions 2