Treatment of Enteric Fever in Children
Azithromycin is the first-line treatment for enteric fever in children, particularly in areas with high fluoroquinolone resistance, due to its superior efficacy, lower risk of clinical failure, and shorter hospital stays compared to other options. 1
First-Line Treatment Options
- Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is recommended as first-line therapy, especially in areas with high fluoroquinolone resistance 1, 2
- Azithromycin has shown a 94% cure rate in children with typhoid fever and has a lower risk of relapse (OR 0.09) compared to ceftriaxone 1, 2
- For severe cases requiring hospitalization, ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is recommended 3, 4
- Once clinical improvement occurs with IV therapy, transition to oral therapy (such as azithromycin) may be considered 4
Treatment Based on Resistance Patterns
- For fully susceptible S. typhi strains, fluoroquinolones (ofloxacin or ciprofloxacin) may be used, but resistance is increasingly common 1
- In a randomized trial comparing oral cefixime for 7 days with oral ofloxacin for 5 days in Vietnamese children with culture-proven typhoid fever, ofloxacin showed significantly fewer treatment failures and shorter duration of fever 5
- However, over 70% of S. typhi isolates in many regions are now resistant to fluoroquinolones, making ceftriaxone or azithromycin better empiric choices 4, 6
- Cefixime can provide a useful alternative treatment for uncomplicated typhoid fever but is less effective than fluoroquinolones in susceptible strains 5
Dosing Guidelines
- Azithromycin: 20 mg/kg/day (maximum 1g/day) orally for 7 days 3, 1
- Ceftriaxone: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 4
- Cefixime: Appropriate oral option when transitioning from IV therapy 7
Special Considerations
- Always obtain blood cultures before starting antibiotics when possible 4
- For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started immediately after collection of blood cultures 1
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1
- Despite susceptibility, clinical non-response may occur in approximately 10% of patients, who may need combinations of antibiotics 7
Emerging Resistance Patterns
- Resistance to fluoroquinolones is essentially a class effect and is increasing globally 5
- A study from Nepal showed that despite global surge of antimicrobial resistance, many Salmonella enterica isolates remained susceptible to conventional antibiotics including chloramphenicol and cefixime 6
- However, another study from India reported 63% resistance to azithromycin among S. typhi isolates, highlighting the importance of local resistance patterns 8
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 4
- Be aware that despite in vitro susceptibility, clinical non-response to third-generation cephalosporins may occur 7
- Consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 3, 6