What are the recommended medications and dosages for treating typhoid fever?

Typhoid Fever Medications

First-Line Treatment Recommendation

Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for adults with typhoid fever, particularly for cases originating from South Asia where fluoroquinolone resistance exceeds 70%. 1, 2, 3

Treatment Algorithm Based on Geographic Origin and Resistance

For Cases from South Asia (High Fluoroquinolone Resistance)

• Start with azithromycin empirically as fluoroquinolone resistance approaches 96% in some South Asian regions 1
• Azithromycin demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1
• Risk of relapse is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 3
• Never use ciprofloxacin empirically for South or Southeast Asian cases due to widespread resistance 1

For Severe or Complicated Cases

• Ceftriaxone 2g IV daily for 14 days is preferred for patients with unstable clinical condition or severe disease 2
• Ceftriaxone is particularly appropriate when oral therapy is not feasible 2
• The 14-day duration reduces relapse risk compared to shorter courses 2

For Confirmed Fluoroquinolone-Sensitive Cases Only

• Ciprofloxacin 500 mg twice daily for 7-10 days can be used when susceptibility is confirmed 4, 5
• Critical caveat: The organism must be sensitive to both ciprofloxacin AND nalidixic acid on disc testing; ciprofloxacin disc testing alone is unreliable 2

Specific Dosing Regimens

Adults

• Azithromycin: 500 mg once daily for 7 days 1, 3
• Ceftriaxone: 2g IV/IM daily for 14 days (severe cases) or 80 mg/kg daily for 5-7 days 4, 2
• Ciprofloxacin (if sensitive): 500 mg twice daily for 10 days 5

Children

• Azithromycin: 20 mg/kg/day (maximum 1g/day) for 7 days 1
• Ceftriaxone: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 4, 1
• Ciprofloxacin (if sensitive): 15 mg/kg twice daily for 7-10 days (maximum 500 mg/dose) 4

Expected Clinical Response and Monitoring

• Expect fever clearance within 4-5 days of appropriate therapy 1
• With azithromycin, mean fever clearance is 5.8 days 6
• With ciprofloxacin (sensitive strains), mean fever clearance is 3.3-4 days 7, 8
• If no clinical improvement by day 5, consider resistance or alternative diagnosis and switch therapy 1
• Obtain blood cultures before starting antibiotics whenever possible, as they have highest yield in the first week 1, 2

Critical Pitfalls to Avoid

Antibiotic Selection Errors

• Do not use cefixime as first-line therapy: documented failure rates of 4-37.6% and relapse rates of 4-37.6% 1
• If cefixime must be used, mandatory test-of-cure at 1 week is required 1
• Avoid empiric ciprofloxacin for cases from endemic areas without confirmed susceptibility 1, 2

Treatment Duration Errors

• Complete the full 7-day course minimum even if fever resolves early 1
• For ceftriaxone, use 14-day course to prevent relapse (occurs in 10-15% of inadequately treated cases) 1, 2
• Premature discontinuation significantly increases relapse risk 1

Management of Treatment Failure

If poor response to azithromycin occurs after 5 days:

• Confirm antimicrobial susceptibility testing if available 3
• Switch to ceftriaxone 2g IV daily 3
• Consider combination therapy with cefixime only as last resort 3

Complications Requiring Surgical Intervention

• Intestinal perforation occurs in 10-15% of patients with illness duration exceeding 2 weeks 1, 2
• Surgical intervention with simple excision and closure is required, with success rates up to 88.2% 1
• Other complications include gastrointestinal bleeding and typhoid encephalopathy 2

Adverse Effects

Azithromycin

• Most common: gastrointestinal symptoms including nausea, vomiting, abdominal pain, and diarrhea 1, 3
• Monitor for QT-prolonging medication interactions 1
• Contraindicated in patients with macrolide hypersensitivity 3

Ciprofloxacin

• Generally well-tolerated when used for appropriate duration 5
• Must be administered at least 2 hours before or 6 hours after antacids, calcium, iron, or zinc products 5

Evidence Quality Considerations

The recommendation for azithromycin over fluoroquinolones is based on:

• Multiple high-quality guidelines from 2025 showing consistent superiority 1, 2, 3
• Meta-analysis demonstrating lower clinical failure rates (OR 0.48) 1
• Dramatically lower relapse rates (OR 0.09) compared to ceftriaxone 1
• However, controlled human infection model data shows azithromycin has prolonged bacteremia clearance (90.8 vs 20.1 hours) compared to ciprofloxacin for sensitive strains 9
• This discrepancy likely reflects the difference between treating resistant strains in clinical practice versus sensitive strains in research settings 9