Treatment of Typhoid Fever
Azithromycin is the recommended first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, with a dose of 500 mg once daily for 7-14 days for adults or 20 mg/kg/day (maximum 1g/day) for children. 1, 2
First-Line Treatment Options
- Azithromycin demonstrates superior outcomes with lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones for uncomplicated typhoid fever 1, 2
- Azithromycin has a significantly lower risk of relapse (OR 0.09) compared to ceftriaxone 3
- For adults, the recommended dose is 500 mg once daily for 7-14 days 1
- For children, the recommended dose is 20 mg/kg/day (maximum 1g/day) for 7-14 days 1
Treatment Algorithm Based on Resistance Patterns
- For fully susceptible S. typhi: Fluoroquinolones remain effective, but azithromycin is still a strong alternative 1, 3
- For multidrug-resistant strains: Azithromycin or ceftriaxone is recommended 1
- For quinolone-resistant strains: Azithromycin is the preferred first-line therapy 2, 3
Alternative Treatment Options
- Ceftriaxone is recommended for severe cases requiring parenteral therapy, at a dose of 1-2g IV/IM daily for adults or 50-80 mg/kg/day for children (maximum 2g/day) for 5-7 days 1, 4
- Once clinical improvement occurs with IV therapy, transition to oral azithromycin may be considered 1
- Ciprofloxacin is FDA-approved for typhoid fever but should not be used empirically for cases originating from South Asia due to high resistance rates 2, 5
Clinical Considerations
- Blood cultures should be obtained before starting antibiotics when possible, as they have the highest yield within the first week of symptom onset 1, 3
- Treatment should be continued for the full course (7-14 days) to prevent relapse 3
- Complications of typhoid fever occur in 10-15% of patients and are more likely if duration of illness exceeds 2 weeks 1, 3
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 2
Complications Management
- In severe cases with intestinal perforation, surgical intervention is recommended 1
- For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started after collection of blood, stool, and urine cultures 2
Important Pitfalls to Avoid
- Do not use ciprofloxacin empirically for cases originating from South Asia due to high resistance rates (>70% of isolates) 2, 6
- Do not discontinue treatment prematurely; complete the full course of antibiotics to prevent relapse 1
- Be aware of increasing resistance to fluoroquinolones, particularly among travelers to South and Southeast Asia 7, 2
- Do not delay surgical intervention in cases with intestinal perforation 1