What is the recommended treatment for a patient with typhoid fever?

Typhoid Fever Treatment

Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for typhoid fever in adults, particularly given the widespread fluoroquinolone resistance exceeding 70% in South Asia where most cases originate. 1

Treatment Algorithm

First-Line Empiric Therapy

• Start azithromycin immediately as empiric therapy for suspected typhoid fever, especially for cases from South Asia where fluoroquinolone resistance approaches 96% in some regions 1
• Dosing:
  • Adults: 500 mg once daily for 7 days 1
  • Children: 20 mg/kg/day (maximum 1g/day) for 7 days 1

Alternative First-Line Option for Severe Cases

• Ceftriaxone is preferred for patients with unstable clinical condition or severe illness 2
• Dosing:
  • Adults: 2g IV daily for 14 days 2
  • Children: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1

Why Azithromycin Over Other Options

• Superior clinical outcomes: Azithromycin demonstrates significantly lower risk of clinical failure (OR 0.48) compared to fluoroquinolones 1
• Shorter hospital stays: Reduces hospitalization by approximately 1 day compared to fluoroquinolones (MD -1.04 days) 1
• Dramatically lower relapse rates: OR 0.09 compared to ceftriaxone 1
• Resistance considerations: Fluoroquinolone resistance exceeds 70% in South Asian isolates, making ciprofloxacin unreliable 1, 2

When to Avoid Fluoroquinolones

• Never use ciprofloxacin empirically for cases from South or Southeast Asia due to resistance rates approaching 96% 1
• Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi, but only when susceptibility is confirmed 3
• If fluoroquinolones must be considered: Only use when culture confirms susceptibility to BOTH ciprofloxacin AND nalidixic acid on disc testing 2
• Geographic restriction: Avoid fluoroquinolones entirely for travel-associated cases from Asia 1, 2

Critical Diagnostic Steps Before Treatment

• Obtain blood cultures immediately before starting antibiotics—they have the highest yield (40-80% sensitivity) within the first week of symptoms 2, 4
• For septic patients: Start broad-spectrum therapy immediately after collecting cultures; do not delay 1
• Bone marrow culture has higher sensitivity (35-65%) if blood cultures are negative 4

Expected Clinical Response and Monitoring

• Fever clearance: Expect defervescence within 4-5 days of appropriate therapy 4, 5
• If no improvement by day 5: Consider antibiotic resistance or alternative diagnosis 1
• Complete the full 7-day course even if fever resolves early—premature discontinuation leads to 10-15% relapse rates 1, 4

Alternative Agents (When First-Line Options Fail or Are Contraindicated)

Cefixime

• Use with extreme caution: Treatment failure rates of 4-37.6% documented in clinical practice 1
• WHO classification: Listed only as "alternative" option, not first-line 1
• Mandatory follow-up: Requires test-of-cure at 1 week due to high failure rates 1

Gatifloxacin

• Newer fluoroquinolone that remains effective in some regions where older fluoroquinolones have failed 1, 6
• Evidence from Vietnam (2004-05): Performed equivalently to azithromycin with no difference in outcomes 1, 6
• Consider only when: Azithromycin and ceftriaxone are not suitable due to allergy or intolerance 1

Levofloxacin

• Highly restricted use: Only when culture confirms fluoroquinolone susceptibility AND case is not from South/Southeast Asia 1
• Treatment failure consequences: Resistant strains result in significantly prolonged illness (76.4 hours vs 41.2 hours for susceptible strains) 1

Common Pitfalls to Avoid

• Do not rely on Widal test: Lacks sensitivity and specificity; not recommended for diagnosis 2, 7
• Do not use ciprofloxacin disc testing alone: Organism must also be sensitive to nalidixic acid to be considered truly fluoroquinolone-sensitive 2
• Do not stop antibiotics when fever resolves: Complete the full course to prevent relapse 1, 4
• Do not use combination typhoid-paratyphoid vaccines: Only monovalent S. typhi preparations should be used 1

Complications Requiring Surgical Intervention

• Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 4
• Management: Requires immediate surgical intervention with simple excision and closure (88.2% success rate) 1
• Other complications: Gastrointestinal bleeding and typhoid encephalopathy occur in 10-15% of cases 2

Adverse Effects of Azithromycin

• Common gastrointestinal symptoms: Nausea, vomiting, abdominal pain, and diarrhea 1
• Monitor for QT prolongation: Particularly with concurrent QT-prolonging medications 1

Prevention Considerations

• Vaccination provides 50-80% protection and does not protect against Salmonella Paratyphi 1, 2
• Ty21a oral vaccine: One capsule on alternate days for total of four doses, booster every 5 years 1
• Parenteral inactivated vaccine: 0.5 ml subcutaneously on two occasions ≥4 weeks apart, booster every 3 years 1
• Food and water safety precautions remain essential even after vaccination 1, 2