What is the dose and duration of cefixime (third-generation cephalosporin) for the treatment of typhoid fever?

Cefixime Dosing for Typhoid Fever

Cefixime is NOT recommended as first-line therapy for typhoid fever; azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days is the preferred treatment, particularly in South Asia where fluoroquinolone resistance exceeds 70%. 1, 2

Why Cefixime Should Be Avoided as First-Line

• Cefixime has documented treatment failure rates of 4-37.6% in clinical practice, making it a poor choice for empiric therapy 1
• The World Health Organization lists cefixime only as an "alternative" option, not first-line, and recommends azithromycin as preferred treatment 1
• If cefixime must be used, a mandatory test-of-cure at 1 week is required due to high failure rates 1
• Cefixime performs worse than fluoroquinolones in head-to-head trials, and fluoroquinolones themselves have lower efficacy than azithromycin (OR 0.48 for clinical failure with azithromycin vs fluoroquinolones) 1

Cefixime Dosing (When Used as Alternative)

If cefixime is selected despite its limitations:

Adults and Children

• Dose: 8 mg/kg/day as a single daily dose (or divided into two doses of 20 mg/kg/day total, maximum 400mg twice daily) 2, 3
• Duration: 7-14 days 2, 3
• The 14-day duration was used in older studies, but 7 days may be adequate for uncomplicated cases 2, 3

Pediatric-Specific Dosing

• 10 mg/kg/day divided every 12 hours for 14 days was used in a randomized trial comparing cefixime to ceftriaxone 3
• Mean time to defervescence was 8.0 ± 4.1 days in the cefixime group 3

Superior First-Line Alternative: Azithromycin

Instead of cefixime, use azithromycin:

• Adults: 500 mg once daily for 7 days 1, 4
• Children: 20 mg/kg/day (maximum 1g/day) for 7 days 1, 2, 4
• Azithromycin demonstrates dramatically lower relapse rates (OR 0.09) compared to ceftriaxone, while cefixime has documented relapse rates of 4-37.6% 1
• Clinical cure rate with azithromycin is 85% compared to 71% with cefixime 5
• Mean fever clearance time with azithromycin (5.8 days) is significantly shorter than cefixime (7.1 days) 5

When to Use Parenteral Ceftriaxone Instead

For severe cases requiring hospitalization:

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1, 2
• Transition to oral therapy (azithromycin preferred) once clinically improved and afebrile for 24 hours 2
• Ceftriaxone remains highly effective with comparable defervescence times to oral agents 3, 6

Critical Pitfalls to Avoid

• Never use ciprofloxacin empirically for cases from South Asia due to resistance rates approaching 96% 1, 2
• Do not rely on cefixime as first-line therapy given its 4-37.6% failure rate 1
• Always obtain blood cultures before starting antibiotics when possible, as they have the highest yield within the first week of symptom onset 1, 2
• Complete the full antibiotic course even if fever resolves early to prevent relapse, which occurs in 10-15% of inadequately treated cases 1
• If using cefixime, mandatory follow-up culture at 1 week is required to confirm treatment success 1

Monitoring Expected Response

• Expect fever clearance within 4-5 days with azithromycin, but 7-8 days with cefixime 1, 5
• If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Monitor for complications (gastrointestinal bleeding, intestinal perforation) which occur in 10-15% of patients, especially with illness duration exceeding 2 weeks 1, 2