What is the treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin is the first-line treatment for typhoid fever, given at 20 mg/kg/day (maximum 1g/day) orally for 7 days in children or 500 mg once daily for 7-14 days in adults, particularly due to widespread fluoroquinolone resistance. 1, 2, 3

First-Line Treatment: Azithromycin

• Azithromycin demonstrates superior outcomes with a 94% cure rate, lower risk of clinical failure (OR 0.48), and significantly lower relapse rates (OR 0.09) compared to ceftriaxone. 1, 3

• The medication also results in shorter hospital stays compared to fluoroquinolones. 2, 3

• Dosing:

  • Adults: 500 mg once daily for 7-14 days 2, 3
  • Children: 20 mg/kg/day (maximum 1g/day) for 7 days 1

• Fever clearance typically occurs within 4-5 days of appropriate therapy. 2, 3

Alternative Treatment Options Based on Clinical Severity and Resistance

For Severe Cases Requiring Hospitalization

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is recommended for severe typhoid requiring parenteral therapy. 1, 2

• Once clinical improvement occurs and temperature has been normal for 24 hours, transition to oral azithromycin. 1, 2

For Fully Susceptible Strains (Rare)

• Fluoroquinolones (ciprofloxacin 500 mg twice daily for 7-14 days) may be used only when susceptibility is confirmed. 4, 5

• However, over 70% of S. typhi isolates are now resistant to fluoroquinolones, making this option increasingly obsolete. 1

Oral Cephalosporin Alternative

• Cefixime 8 mg/kg/day as a single daily dose for 7-14 days can be used as an oral option, though it may not perform as well as azithromycin. 1, 6

Critical Treatment Considerations

Resistance Patterns

• Fluoroquinolone resistance is particularly problematic in South and Southeast Asia, with over 93.5% of isolates showing nalidixic acid resistance (a marker for decreased ciprofloxacin susceptibility). 7, 8, 5

• Ciprofloxacin should not be used empirically for cases originating from India, Pakistan, or Southeast Asia. 7, 3

• Extensively drug-resistant strains have emerged in Pakistan, showing resistance to both fluoroquinolones and ceftriaxone. 5, 6

Diagnostic Approach

• Always obtain blood cultures before starting antibiotics when possible, as they have the highest yield within the first week of symptom onset. 2

• For patients with clinical features of sepsis, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures. 1, 2

Monitoring and Duration

• Complete the full 7-day course of antibiotics to prevent relapse, which occurs in 10-15% of untreated or inadequately treated patients. 2

• Monitor for fever clearance within 4-5 days; if no improvement, consider resistance or complications. 2, 3

• Watch for complications including intestinal perforation, which occurs more frequently if illness duration exceeds 2 weeks and requires surgical intervention. 2

Common Pitfalls to Avoid

• Do not use ciprofloxacin empirically without susceptibility testing, especially for travel-related cases from South Asia. 3, 5

• Do not discontinue treatment prematurely even if clinical improvement occurs; complete the full course to prevent relapse. 2

• Do not delay surgical consultation if intestinal perforation is suspected, as simple excision and closure is effective in up to 88.2% of cases. 2

• Be aware that azithromycin can cause gastrointestinal adverse effects (nausea, vomiting, abdominal pain, diarrhea) and has potential drug interactions. 2, 3

Treatment Algorithm Summary

1. Uncomplicated typhoid fever: Start azithromycin 20 mg/kg/day (max 1g) for 7 days 1, 3
2. Severe cases/sepsis: Start IV ceftriaxone 50-80 mg/kg/day, transition to oral azithromycin when stable 1, 2
3. Confirmed susceptible strains only: Consider fluoroquinolones or cefixime 1, 4
4. Quinolone-resistant strains: Azithromycin or ceftriaxone 2, 3