Recommended Treatment for Typhoid Fever
For typhoid fever, azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line treatment in regions with high fluoroquinolone resistance, particularly for patients returning from South Asia, while intravenous ceftriaxone 2g daily for 14 days should be used for severe or complicated cases. 1, 2
Treatment Selection Based on Geographic Origin and Severity
For Uncomplicated Typhoid Fever
Azithromycin is the optimal first-line choice for most cases, particularly when patients have traveled to or reside in South Asia where fluoroquinolone resistance exceeds 70%. 1, 2 The recommended regimen is:
- Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 2
- This achieves a 94% cure rate in children and demonstrates superior outcomes with lower clinical failure rates (OR 0.48) and significantly lower relapse risk (OR 0.09) compared to ceftriaxone 2
- Azithromycin also results in shorter hospital stays compared to fluoroquinolones 2
Alternative oral option for uncomplicated cases:
- Cefixime 8 mg/kg/day as a single daily dose for 7-14 days can be used when azithromycin is not available or contraindicated 2
For Severe or Complicated Typhoid Fever
Intravenous ceftriaxone is the treatment of choice for hospitalized patients:
- Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days 2
- The standard adult dose is 2g IV daily for 14 days to reduce relapse risk 1
- Transition to oral therapy (azithromycin or cefixime) once the patient is clinically improved and afebrile for 24 hours 2
Critical Geographic Considerations
Fluoroquinolones should be avoided as first-line therapy in patients with exposure to South Asia due to resistance rates exceeding 70% in isolates imported from this region. 1 Even when considering ciprofloxacin:
- The FDA approves ciprofloxacin for typhoid fever caused by Salmonella typhi 3
- However, ciprofloxacin disc testing alone is unreliable; the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1
- Do not use ciprofloxacin empirically for cases originating from India or South Asia 2
Diagnostic Approach Before Treatment
Obtain blood cultures before initiating antibiotics whenever possible:
- Blood cultures have the highest yield (40-80% sensitivity) within the first week of symptom onset 1, 2
- Stool and urine cultures become positive after the first week, with lower sensitivities of 35-65% and 0-58%, respectively 1
- Bone marrow cultures have higher sensitivity than blood cultures but are rarely practical 1
- The serological Widal test lacks sensitivity and specificity and is not recommended 1
Expected Clinical Response and Monitoring
Fever should clear within 4-5 days of appropriate therapy:
- Monitor for clinical response with expected defervescence by day 4-5 2
- Lack of fever clearance by this timeframe should prompt reassessment for complications or treatment failure 2
Watch for complications, which occur in 10-15% of patients:
- Gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy are more likely if illness duration exceeds 2 weeks before treatment 1, 2
- These complications necessitate immediate escalation to intravenous ceftriaxone if not already initiated 1
Common Pitfalls to Avoid
Do not rely on vaccination history to exclude typhoid fever:
- Previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid fever 1, 2
Do not assume fluoroquinolone susceptibility based on clinical response alone:
- Even in regions outside South Asia, verify nalidixic acid sensitivity before considering fluoroquinolones as definitive therapy 1
Do not use inadequate treatment durations:
- While 7-day courses of azithromycin are effective, ceftriaxone requires 14 days to minimize relapse risk 1
Prevention Considerations
Vaccination is recommended for travelers to endemic areas: