What is the treatment for typhoid fever?

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Treatment of Typhoid Fever

First-Line Treatment Recommendation

Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for typhoid fever in adults, particularly given widespread fluoroquinolone resistance exceeding 70% in endemic regions. 1, 2, 3

For children, use azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days. 1, 2

Treatment Algorithm Based on Clinical Presentation and Geography

Step 1: Obtain Blood Cultures Before Starting Antibiotics

  • Collect blood cultures immediately, as they have the highest yield (40-80% sensitivity) within the first week of symptom onset. 1, 2
  • Do not delay antibiotic therapy in severely ill patients; start empiric treatment after collecting cultures. 1, 3

Step 2: Initiate Empiric Therapy with Azithromycin

  • Start azithromycin 500 mg once daily for 7 days in adults. 1, 2, 3
  • For children: azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days. 1, 2
  • Azithromycin demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones. 1, 2
  • Hospital stays are approximately 1 day shorter with azithromycin (mean difference -1.04 days). 1, 2
  • Relapse risk is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone. 1, 2, 3

Step 3: Alternative Therapy for Severe Cases Requiring IV Treatment

  • Use ceftriaxone 1-2g IV/IM daily for 5-7 days in adults. 1, 3
  • For children: ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days. 1
  • Transition to oral therapy when clinically improved. 3

Step 4: Adjust Based on Culture Results and Susceptibility

  • If isolates show full susceptibility (rare), fluoroquinolones (ofloxacin or ciprofloxacin) may be used. 3
  • For quinolone-resistant strains (most common), continue azithromycin or use ceftriaxone/cefixime. 3

Geographic Resistance Patterns: Critical Considerations

South and Southeast Asia

  • Never use ciprofloxacin empirically for cases from South or Southeast Asia. 1, 3
  • Fluoroquinolone resistance exceeds 70% in South Asia, with some regions approaching 96%. 1, 2, 3
  • Over 70% of S. typhi and S. paratyphi isolates imported into the UK from these regions are fluoroquinolone-resistant. 2
  • In Thailand, 93% of isolates were ciprofloxacin-resistant. 1

Resistance Testing Pitfalls

  • Ciprofloxacin disc testing is unreliable for determining sensitivity. 2
  • Only isolates also sensitive to nalidixic acid should be considered fluoroquinolone-sensitive. 2
  • Resistance to nalidixic acid is a marker for decreased ciprofloxacin susceptibility. 4

Monitoring and Expected Clinical Response

Timeline for Improvement

  • Expect fever clearance within 4-5 days of appropriate antibiotic therapy. 1, 2, 3
  • If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis. 1

Complete the Full Course

  • Complete the full 7-day course even if fever resolves early to prevent relapse. 1
  • Relapse occurs in 10-15% of inadequately treated cases. 1

Common Adverse Effects

Azithromycin

  • Gastrointestinal symptoms are most common: nausea, vomiting, abdominal pain, and diarrhea. 1, 2, 3
  • Monitor for potential drug interactions, particularly with QT-prolonging medications. 1, 3

Critical Pitfalls to Avoid

Do Not Use Fluoroquinolones Empirically

  • Avoid empiric ciprofloxacin use for cases from South Asia due to resistance rates approaching 96%. 1
  • Treatment failure with fluoroquinolones in resistant strains results in significantly prolonged illness (76.4 hours vs 41.2 hours for susceptible strains). 1
  • Fluoroquinolone-resistant typhoid treated with fluoroquinolones shows suboptimal clinical outcomes. 1

Cefixime Has High Failure Rates

  • Cefixime has documented treatment failure rates of 4-37.6% in clinical practice. 1
  • If cefixime must be used, a mandatory test-of-cure at 1 week is required. 1
  • The WHO lists cefixime only as an "alternative" option, not first-line. 1

Do Not Discontinue Antibiotics Prematurely

  • Complete the full course even if fever resolves early to prevent relapse. 1

Management of Complications

Intestinal Perforation

  • Occurs in 10-15% of patients with illness duration exceeding 2 weeks. 1
  • Surgery is the treatment of choice for small bowel perforations. 4
  • Primary repair or resection with primary anastomosis is recommended depending on tissue viability. 4
  • Mortality rate for typhoid ileal perforations can reach up to 60%. 4

Prevention Strategies

Vaccination

  • Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa). 4, 1, 2
  • Two vaccines available: Ty21a oral vaccine (one capsule on alternate days for 4 doses) and Vi-polysaccharide parenteral vaccine (0.5 mL subcutaneously). 4, 1
  • Booster doses: every 5 years for oral vaccine, every 2-3 years for parenteral vaccine. 4, 1
  • Vaccination provides only 50-80% protection and does not protect against Salmonella Paratyphi. 4, 1, 2, 3

Hand Hygiene and Food Safety

  • Hand hygiene and appropriate food/water safety practices remain essential despite vaccination. 4, 1

References

1
Guideline

Management of Typhoid Fever

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Management of Typhoid Fever

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

3
Guideline

Management of Typhoid Fever

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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