What is the drug of choice for typhoid fever in children?

Drug of Choice for Typhoid Fever in Children

Azithromycin at 20 mg/kg/day (maximum 1g/day) orally for 7 days is the drug of choice for typhoid fever in children, particularly given the widespread fluoroquinolone resistance now exceeding 70% in most endemic regions. 1, 2

Treatment Algorithm Based on Clinical Severity

Uncomplicated Typhoid Fever (Outpatient or Mild Cases)

• Start with oral azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days as first-line therapy 3, 1, 2
• Azithromycin demonstrates a 94% cure rate in children with significantly lower relapse risk (OR 0.09) compared to ceftriaxone 1, 2, 4
• Clinical failure risk is also lower with azithromycin (OR 0.48) compared to fluoroquinolones, with shorter hospital stays by approximately 1 day 1, 5

Severe Typhoid Fever (Hospitalized or Complicated Cases)

• Use ceftriaxone 50-80 mg/kg/day IV (maximum 2g/day) for 5-7 days initially 3, 1, 2
• Transition to oral azithromycin once the child is clinically improved and afebrile for 24 hours 2
• Expect fever clearance within 4-5 days of appropriate therapy 1, 2

Why Fluoroquinolones Are No Longer First-Line

Never use ciprofloxacin empirically for typhoid fever in children, especially for cases from South Asia where resistance rates approach 96%. 1, 2 While older guidelines listed ciprofloxacin 15 mg/kg twice daily for 7-10 days 3, this recommendation is now obsolete due to widespread resistance 1, 5. Fluoroquinolones should only be considered when susceptibility is confirmed by culture 1, 5.

Critical Diagnostic Steps Before Treatment

• Obtain blood cultures before starting antibiotics whenever possible, as they have the highest yield within the first week of symptom onset 1, 2, 5
• Blood cultures remain the gold standard, while stool and urine cultures become positive only after the first week 2
• For children presenting with sepsis features, start broad-spectrum therapy immediately after collecting cultures 1

Alternative Treatment Options

Second-Line Oral Option

• Cefixime 8 mg/kg/day as a single daily dose for 7-14 days can be used if azithromycin is unavailable 2, 6
• Cefixime shows comparable efficacy to ceftriaxone with the advantage of oral administration 6

When Azithromycin Fails

• If no clinical response by day 5, consider drug resistance or alternative diagnosis 1
• Switch to ceftriaxone 50-80 mg/kg/day IV for 5-7 days 1, 2

Dosing Summary Table

Drug	Dose	Duration	Route	Clinical Setting
Azithromycin	20 mg/kg/day (max 1g)	7 days	Oral	First-line for uncomplicated cases [1,2]
Ceftriaxone	50-80 mg/kg/day (max 2g)	5-7 days	IV/IM	Severe cases or treatment failure [1,2]
Cefixime	8 mg/kg/day	7-14 days	Oral	Alternative if azithromycin unavailable [2]

Common Pitfalls to Avoid

• Never discontinue antibiotics prematurely even if fever resolves early; complete the full 7-day course to prevent relapse, which occurs in 10-15% of inadequately treated cases 1
• Do not rely on clinical presentation alone for diagnosis; blood cultures are essential as typhoid fever mimics many other febrile illnesses 2
• Avoid ciprofloxacin for empiric therapy in children from endemic areas without confirmed susceptibility 1, 2

Monitoring and Expected Clinical Response

• Fever should clear within 4-5 days of starting appropriate antibiotic therapy 1, 2
• Mean defervescence time with ceftriaxone is approximately 4-5 days 7
• With azithromycin, clinical cure is achieved in 91-94% of children 4, 8
• Monitor closely for complications (gastrointestinal bleeding, intestinal perforation, encephalopathy) which occur in 10-15% of patients, especially if illness duration exceeds 2 weeks 1, 2, 5

Adverse Effects to Monitor

• Azithromycin: gastrointestinal symptoms including nausea, vomiting, abdominal pain, and diarrhea are most common 1
• Monitor for QT prolongation, especially if the child is on other QT-prolonging medications 1
• Ceftriaxone: generally well-tolerated with minimal adverse effects in children 7, 4

Why This Represents a Shift from Older Guidelines

The evidence clearly shows that resistance patterns have fundamentally changed typhoid treatment. While guidelines from the 1990s recommended chloramphenicol or ciprofloxacin 3, current high-quality evidence from multiple sources demonstrates azithromycin's superiority in the modern resistance landscape 1, 2, 5. The WHO Pocket Book recommendations from 2015 listing ciprofloxacin as first-line 3 are now outdated given resistance data showing >70% fluoroquinolone resistance in endemic regions 1, 5.