What is the recommended treatment for typhoid fever?

Treatment for Typhoid Fever

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 South Asia. 1, 2

First-Line Treatment Regimen

• Azithromycin is the drug of choice for empiric treatment of typhoid fever, especially for cases originating from South Asia where fluoroquinolone resistance approaches 96% in some regions 1, 2
• Adult dosing: Azithromycin 500 mg once daily orally for 7-14 days 1, 2, 3
• Pediatric dosing: Azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days 1, 2

Why Azithromycin Over Other Options

Azithromycin demonstrates superior clinical outcomes compared to alternatives:

• Lower clinical failure rate: OR 0.48 (95% CI 0.26-0.89) compared to fluoroquinolones 1, 2
• Shorter hospital stays: Approximately 1 day shorter than fluoroquinolones (mean difference -1.04 days) 1, 2
• Dramatically lower relapse risk: OR 0.09 (95% CI 0.01-0.70) compared to ceftriaxone 1, 2
• Faster fever clearance: Mean 5.8 days with azithromycin versus 7.1 days with cefixime and 8.2 days with ciprofloxacin 4

Alternative Treatment Options (When Azithromycin Cannot Be Used)

Ceftriaxone

• Adult dosing: 1-2g IV/IM daily for 5-7 days 1
• Pediatric dosing: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1
• Use for severe cases or when oral therapy is not feasible 3
• May have higher relapse rates compared to azithromycin 1

Fluoroquinolones (Only if Susceptibility Confirmed)

• Ciprofloxacin or ofloxacin remain effective when susceptibility is documented 1, 5
• Critical caveat: Ciprofloxacin is FDA-approved for typhoid fever but shows 18.1% resistance rates in some studies 5, 6
• The FDA label indicates ciprofloxacin for typhoid fever caused by Salmonella typhi, but this predates widespread resistance 5

Treatment Algorithm Based on Geographic Origin

For cases from South or Southeast Asia:

• Start azithromycin immediately - do NOT use ciprofloxacin empirically 1, 2
• Fluoroquinolone resistance exceeds 70% and approaches 96% in these regions 1, 2

For cases from other regions with known susceptibility:

• Fluoroquinolones may be considered if local resistance patterns permit 1, 3
• Always obtain blood cultures before starting antibiotics when possible 1, 2

Critical Diagnostic Steps

• Obtain blood cultures before initiating antibiotics - highest yield within the first week of symptom onset 1, 2
• For patients with sepsis features, start broad-spectrum therapy immediately after collecting cultures 1, 3
• Blood or bone marrow culture remain the reference standard despite low sensitivity of blood culture 7

Expected Clinical Response and Monitoring

• Fever should clear within 4-5 days of appropriate antibiotic therapy 1, 2, 3
• If no clinical improvement by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Monitor for common azithromycin adverse effects: nausea, vomiting, abdominal pain, and diarrhea 1, 2, 3
• Watch for QT-prolonging drug interactions with azithromycin 1, 2

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely - complete the full 7-day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 1, 2, 3
• Never use ciprofloxacin empirically for South/Southeast Asian cases - resistance is nearly universal 1, 2, 3
• Avoid cefixime as first-line therapy - documented treatment failure rates of 4-37.6% and requires mandatory test-of-cure at 1 week if used 1, 8
• Do not use combination typhoid-paratyphoid vaccines; only monovalent S. typhi preparations should be used 9, 1

Management of Complications

• Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 2
• Requires immediate surgical intervention with simple excision and closure, successful in up to 88.2% of cases 1, 2
• Watch for life-threatening complications that can arise in the second week of untreated illness 7

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) 9, 1, 2
• Two vaccine types available: Ty21a oral vaccine (4 doses on alternate days, refrigerated) and Vi-polysaccharide parenteral vaccine 9, 1
• Important limitation: Vaccination provides only 50-80% protection and does NOT protect against Salmonella Paratyphi 1, 2, 7
• Ty21a oral vaccine requires booster every 5 years; parenteral vaccine every 3 years 1
• Hand hygiene and food/water safety precautions remain essential and cannot be replaced by vaccination alone 1, 2