What is the recommended dose of cefixime (a third-generation cephalosporin antibiotic) for a pediatric patient diagnosed with typhoid fever?

Cefixime Dosing for Typhoid Fever in Pediatric Patients

For pediatric patients with typhoid fever, administer cefixime at 8-10 mg/kg/day divided into two doses (every 12 hours) for 7-14 days, with the FDA-approved maximum daily dose of 8 mg/kg/day for general pediatric use, though higher doses (10-20 mg/kg/day) have been studied specifically for typhoid fever. 1, 2, 3

FDA-Approved Dosing Framework

The FDA label establishes the baseline pediatric dosing for cefixime:

• Standard dose: 8 mg/kg/day administered as a single daily dose or divided into 4 mg/kg every 12 hours 1
• Maximum daily dose for children ≥45 kg or >12 years: 400 mg (adult dose) 1
• The suspension formulation is preferred for pediatric use and achieves higher peak blood levels than tablets 1

Typhoid Fever-Specific Dosing from Clinical Trials

Higher doses have been evaluated specifically for typhoid fever in children, with evidence supporting 10-20 mg/kg/day:

• 10 mg/kg/day divided every 12 hours for 14 days was directly compared to ceftriaxone and showed equivalent efficacy (comparable defervescence times of ~8 days in both groups) 3
• 20 mg/kg/day divided twice daily demonstrated 95% clinical cure rates in an 8-day short-course regimen for multidrug-resistant typhoid 2
• A 7-day course at 20 mg/kg/day in two divided doses showed slower fever clearance (median 8.5 days) compared to ofloxacin but remained effective, with 75% cure rate 4

Treatment Duration Considerations

Duration should be 7-14 days based on clinical response and drug resistance patterns:

• 14-day courses are more established and showed 90-93% cure rates in comparative trials 5, 3
• 8-day short courses (20-30 mg/kg/day) demonstrated 95% efficacy for multidrug-resistant strains with only 1.7% relapse rate 2
• 7-day courses are the minimum effective duration but may have higher failure rates (25% treatment failures with 20 mg/kg/day) 4

Practical Dosing Algorithm

For multidrug-resistant typhoid fever (most common scenario):

1. Start with 10-15 mg/kg/day divided every 12 hours (balancing FDA guidance with typhoid-specific evidence) 1, 2, 3
2. Plan for 10-14 days of therapy initially 2, 3
3. If fever persists beyond 5-7 days, consider switching to alternative therapy (ceftriaxone or azithromycin) 3, 4

For drug-susceptible strains (rare):

• Standard FDA dosing of 8 mg/kg/day may be adequate, but higher doses are reasonable given the severity of typhoid fever 1

Important Clinical Caveats

• Cefixime shows slower fever clearance (median 8-9 days) compared to fluoroquinolones (4-5 days), so delayed defervescence does not necessarily indicate treatment failure 4
• Monitor for treatment failure if fever persists beyond 10 days or clinical deterioration occurs; approximately 10-25% may require therapy change depending on resistance patterns 3, 4
• Relapse rates are low (1.7-8%) but can occur up to 21 days post-therapy, requiring clinical follow-up 2, 3
• Mild gastrointestinal side effects (nausea/vomiting 8%, loose stools 6%) are common but may be difficult to distinguish from typhoid symptoms 2
• The suspension must specify concentration (100 mg/5 mL or 200 mg/5 mL) to avoid dosing errors 1