What antibiotics and for how long should they be continued in a proven case of typhoid (Salmonella Typhi infection) in India?

Treatment of Typhoid Fever in India

For proven cases of typhoid fever in India, azithromycin (20 mg/kg/day for 7 days) or ceftriaxone (50-80 mg/kg/day for 7 days) are the recommended first-line treatments due to high rates of fluoroquinolone resistance in the region. 1

Antibiotic Selection Algorithm

First-line options:

1. Azithromycin

   • Dosage: 20 mg/kg/day (maximum 1g/day) orally once daily
   • Duration: 5-7 days
   • Advantages: Excellent safety profile, effective against fluoroquinolone-resistant strains, suitable for children and pregnant women 1

2. Ceftriaxone

   • Dosage: 50-80 mg/kg/day IV (maximum 2g/day)
   • Duration: 7-10 days
   • Advantages: High efficacy, suitable for severe infections or when oral therapy isn't possible 2, 1

Second-line options (if susceptibility confirmed):

• Ciprofloxacin (only if susceptibility confirmed)
  • Dosage: 15 mg/kg twice daily (maximum 500 mg twice daily)
  • Duration: 7-10 days 2, 3
  • Note: High resistance rates in India limit usefulness

Resistance Patterns in India

The choice of antibiotic should consider the high prevalence of resistance in the region:

• Fluoroquinolone resistance: Extremely common in South Asia, with studies showing 97.8% of S. Typhi isolates resistant or intermediately susceptible to ciprofloxacin 4
• Multidrug-resistant (MDR) strains: Resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole
• Nalidixic acid resistance: A marker for decreased ciprofloxacin susceptibility, has increased from 19% to 59% 1

Treatment Duration

The optimal duration of therapy depends on the antibiotic used and clinical response:

• Azithromycin: 5-7 days 1
• Ceftriaxone: 7-10 days for uncomplicated cases 2, 1
• Ciprofloxacin: 10 days (if susceptibility confirmed) 3

Treatment should be continued for the full course even if symptoms resolve earlier to prevent relapse 1.

Special Considerations

Severe Infections

• For severe infections or patients unable to take oral medications, start with IV ceftriaxone (50-80 mg/kg/day) 2
• Once clinical improvement occurs, consider switching to oral therapy to complete the course

Children

• Azithromycin is the preferred option for children due to its safety profile 1
• Fluoroquinolones should be avoided in children when possible due to potential effects on cartilage development

Monitoring Response

• Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy 1
• Fever clearance time is typically 3-5 days with effective therapy
• If no improvement after 72 hours, consider alternative diagnosis or antibiotic resistance

Pitfalls and Caveats

1. Avoid empiric fluoroquinolones in India due to high resistance rates unless susceptibility is confirmed 1, 4

2. Complete the full course of antibiotics even if symptoms resolve quickly to prevent relapse 1

3. Avoid antimotility agents like loperamide in patients with typhoid fever, as they may worsen outcomes 2

4. Consider local resistance patterns when selecting therapy, as they continue to evolve 4

5. Monitor for bone marrow suppression with chloramphenicol if this older agent is used due to susceptibility patterns 5

The emergence of extensively drug-resistant (XDR) typhoid strains in parts of South Asia makes it essential to base treatment on local susceptibility patterns and to use appropriate antibiotics at adequate doses for the full recommended duration.