Treatment of Typhoid Fever
Azithromycin 500 mg once daily for 7 days is the recommended first-line treatment for adults with typhoid fever, particularly given widespread fluoroquinolone resistance. 1, 2, 3
First-Line Treatment Recommendations
Adults
- Azithromycin 500 mg orally once daily for 7 days is the preferred empiric therapy 2, 3
- This recommendation is based on superior outcomes including lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones 3
- Azithromycin demonstrates lower relapse rates (OR 0.09) compared to ceftriaxone 1, 3
Children
- Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2
- This achieves a 94% cure rate in pediatric typhoid fever 1
Severe Cases Requiring Hospitalization
- Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days in children 1
- Ceftriaxone 1-2g IV/IM daily for adults 2
- Transition to oral azithromycin once clinical improvement occurs and temperature has been normal for 24 hours 1, 2
Treatment Algorithm Based on Resistance Patterns
High Fluoroquinolone Resistance Areas (>70% of isolates)
- Use azithromycin or ceftriaxone as empiric therapy 1, 3
- Avoid ciprofloxacin empirically for cases from South Asia due to high resistance rates 3
Fully Susceptible S. typhi (Rare)
- Fluoroquinolones (ofloxacin or ciprofloxacin) may be used if susceptibility is confirmed 1, 3
- However, azithromycin remains a strong alternative even for susceptible strains 2
Multidrug-Resistant Strains
- Azithromycin or ceftriaxone are recommended 2
Alternative Oral Option
- Cefixime 8 mg/kg/day as a single daily dose for 7-14 days in children over 28 days old 1
- Cefixime 400 mg orally once daily for adults 1
- Note: Cefixime may have increased clinical failure, microbiological failure, and relapse compared to fluoroquinolones, with longer fever clearance time (mean difference 1.74 days) 4
Critical Clinical Considerations
Diagnostic Approach
- Obtain blood cultures before starting antibiotics whenever possible 1, 2
- Blood cultures have highest yield within the first week of symptom onset 2
Monitoring Response
- Expect fever clearance within 4-5 days of appropriate therapy 1, 2, 3
- If no improvement by day 5, consider treatment failure and reassess 1
Complications
- Occur in 10-15% of patients, more likely if illness duration exceeds 2 weeks 2
- Intestinal perforation requires immediate surgical intervention with simple excision and closure reported in up to 88.2% of cases 2
Common Pitfalls to Avoid
- Do not use ciprofloxacin empirically without susceptibility testing, especially for infections acquired in South or Southeast Asia where resistance exceeds 70% 1, 3
- Do not discontinue treatment prematurely—complete the full 7-day course to prevent relapse 2
- Do not delay surgical consultation if intestinal perforation is suspected 2
- Do not rely solely on clinical presentation—obtain cultures to confirm diagnosis and guide therapy 1
Adverse Effects of Azithromycin
- Common gastrointestinal symptoms include nausea, vomiting, abdominal pain, and diarrhea 2, 3
- Monitor for potential drug interactions 2, 3