What are the recommended antibiotic regimens for treating typhoid fever?

Recommended Antibiotic Regimens for Typhoid Fever

The most effective first-line treatment for typhoid fever is azithromycin, particularly in areas with increasing fluoroquinolone resistance, due to its safety profile and lower risk of clinical failure. 1

First-Line Treatment Options

For Adults:

• Azithromycin: Preferred option, especially in areas with fluoroquinolone resistance
• Ceftriaxone: 50-80 mg/kg/day IV (maximum 2g/day) for 7-10 days 1, 2
• Ciprofloxacin: 500 mg PO twice daily for 7-10 days (only if susceptibility is confirmed) 3

For Children:

• Azithromycin: First choice, especially for children due to safety profile 1
• Ceftriaxone: 50-60 mg/kg/day IV in two divided doses 2
• Ciprofloxacin: 15 mg/kg twice daily (maximum 500 mg twice daily) for 7-10 days (with caution due to concerns about joint effects) 1, 3

Treatment Selection Algorithm

1. Consider local resistance patterns:

   • In areas with high fluoroquinolone resistance (especially South and Southeast Asia): Use azithromycin or ceftriaxone
   • In areas with confirmed fluoroquinolone susceptibility: Ciprofloxacin may be used

2. Consider patient factors:

   • Pregnant women: Azithromycin or ceftriaxone (avoid fluoroquinolones) 1
   • Children: Azithromycin preferred (avoid fluoroquinolones when possible) 1
   • Severe infection or inability to take oral medications: Ceftriaxone IV 1, 2

3. Treatment duration:

   • Uncomplicated typhoid: 7-10 days 1, 3
   • Severe infections: 10-14 days 1, 3
   • Complete full course even if symptoms resolve earlier 1

Antibiotic Selection Based on Resistance Patterns

Strain Type	First Choice	Alternative Options
Fully sensitive	Azithromycin	Fluoroquinolones, chloramphenicol, amoxicillin, TMP-SMX
Multidrug-resistant	Azithromycin or ceftriaxone	Fluoroquinolones (if susceptible)
Quinolone-resistant	Azithromycin or ceftriaxone	Cefixime

Important Clinical Considerations

• Monitor for clinical response: Improvement typically occurs within 48-72 hours of starting appropriate therapy 1
• Avoid antimotility agents like loperamide, which may worsen outcomes 1
• Fluoroquinolone resistance concerns: Nalidixic acid resistance (a marker for decreased ciprofloxacin susceptibility) increased from 19% in 1999 to 59% in 2008 1
• Cefixime limitations: May have higher failure rates compared to other options and may not perform as well as fluoroquinolones 4

Evidence Strength and Recommendations

The most recent evidence from the Cochrane database (2022) suggests that ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects 4. However, older studies from the 1990s showed that fluoroquinolones like ofloxacin achieved 100% cure rates without relapse 5.

The increasing resistance to fluoroquinolones, particularly in South and Southeast Asia, has led to a shift toward azithromycin and ceftriaxone as preferred treatments 1, 6. For ceftriaxone, some evidence suggests that higher doses (not less than 3g once daily) or longer treatment periods may be needed to reduce relapse rates 5.

Treatment Response Expectations

• Clinical improvement typically within 48-72 hours of starting appropriate therapy 1
• Complete resolution of fever usually within 4-5 days 2
• Treatment should be continued for the full course even if symptoms resolve earlier 1

Remember that antimicrobial resistance patterns continue to evolve, making it essential to consider local resistance patterns when selecting therapy and to use appropriate antibiotics at adequate doses for the full recommended duration.