What is the recommended treatment for typhoid fever in pediatric patients?

Treatment of Typhoid Fever in Pediatric Patients

The recommended first-line treatment for typhoid fever in pediatric patients is azithromycin at 20 mg/kg/day (maximum 1g/day) orally for 7 days, especially in areas with high fluoroquinolone resistance. 1

First-Line Treatment Options

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is recommended as first-line therapy, with a documented 94% cure rate in children and lower risk of relapse compared to ceftriaxone 1
• For severe cases requiring hospitalization, ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is recommended 1, 2
• A 5-day course of azithromycin has been shown to be effective for uncomplicated typhoid fever in children and adolescents with a 94% cure rate 3

Treatment Based on Resistance Patterns

• For fully susceptible S. typhi strains (increasingly rare), fluoroquinolones may be considered, though resistance is becoming common globally 1
• For multidrug-resistant strains: fluoroquinolone (if susceptible) or cefixime, with azithromycin as an alternative 4
• For quinolone-resistant strains (>70% of isolates in many regions): azithromycin or ceftriaxone is recommended as first-line therapy 4, 1

Specific Antibiotic Regimens

Azithromycin

• Dosing: 20 mg/kg/day (maximum 1g/day) orally for 7 days 1
• Benefits: Lower relapse rates compared to ceftriaxone (OR 0.09) 4
• No relapses were observed in a study comparing azithromycin to ceftriaxone in children 3

Ceftriaxone

• Dosing: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 5, 2
• A flexible-duration approach (continuing until defervescence plus 5 additional days) has shown good results with no relapses 6
• Mean defervescence time with ceftriaxone is approximately 5.4 days 6

Cefixime

• Dosing: 10 mg/kg/day divided every 12 hours for 14 days 7
• Can be as effective as parenteral ceftriaxone for uncomplicated cases 7
• Time to defervescence is comparable to ceftriaxone (approximately 8 days) 7

Ciprofloxacin (only if susceptibility confirmed)

• Dosing: 15 mg/kg twice daily for 7-10 days 5
• Should be avoided empirically in cases originating from South Asia due to high resistance rates 1
• For severe cases, initial IV dosing at 10 mg/kg/day has shown 94.4% efficacy in children 8

Treatment Algorithm

1. For uncomplicated typhoid fever:

   • First choice: Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 1
   • Alternative: Cefixime 10 mg/kg/day divided every 12 hours for 14 days (if azithromycin unavailable) 7

2. For severe cases requiring hospitalization:

   • First choice: Ceftriaxone 50-80 mg/kg/day IV for 5-7 days 5, 2
   • Consider transition to oral therapy once clinical improvement occurs 2
   • Alternative approach: Continue ceftriaxone until defervescence plus 5 additional days 6

3. For multidrug-resistant typhoid with confirmed susceptibility:

   • Consider ciprofloxacin 15 mg/kg twice daily for 7-10 days only if susceptibility is confirmed 5, 1

Important Clinical Considerations

• Always obtain blood cultures before starting antibiotics when possible, as they have the highest yield within the first week of symptom onset 4, 2
• Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1
• Complications of typhoid fever (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) occur in 10-15% of patients and are more likely if duration of illness exceeds 2 weeks 4
• Resistance to fluoroquinolones is essentially a class effect and is increasing globally, making them less reliable as empiric therapy 1

Common Pitfalls to Avoid

• Avoid using ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 1
• Do not rely solely on clinical presentation for diagnosis; obtain cultures whenever possible 1
• Consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1
• Be aware that vaccination provides incomplete protection against typhoid fever and does not protect against paratyphoid 4