What is the recommended treatment regimen for typhoid fever?

Recommended Treatment Regimen for Typhoid Fever

First-Line Treatment

Azithromycin 500 mg once daily for 7-14 days is the preferred first-line treatment for adults with typhoid fever, particularly given widespread fluoroquinolone resistance exceeding 70% in endemic regions like South Asia. 1, 2

For children, use azithromycin 20 mg/kg/day (maximum 1g/day) for 7-14 days. 1, 2

Treatment Algorithm Based on Clinical Presentation

Uncomplicated Typhoid Fever

• Start azithromycin 500 mg once daily orally for 7-14 days as empiric therapy 1, 2
• Obtain blood cultures before initiating antibiotics when possible, as they have highest yield within the first week of symptoms (sensitivity 40-80%) 2, 3
• Expect fever clearance within 4-5 days of appropriate therapy 1, 2
• Complete the full 7-14 day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 2

Severe or Unstable Disease

• Use intravenous ceftriaxone 2g IV daily for adults for 14 days 3
• For children: ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1
• This is particularly important for patients with sepsis features or those unable to tolerate oral therapy 1

Why Azithromycin Over Other Options

Superior to Fluoroquinolones

• Fluoroquinolone resistance exceeds 70% in South Asia and approaches 96% in some regions 1, 2
• Azithromycin demonstrates lower risk of clinical failure (OR 0.48,95% CI 0.26-0.89) compared to fluoroquinolones 1
• Hospital stays are approximately 1 day shorter with azithromycin (mean difference -1.04 days) 1, 2
• Never use ciprofloxacin empirically for travel-associated cases from South or Southeast Asia—resistance is nearly universal 1, 2, 4

Superior to Ceftriaxone for Uncomplicated Disease

• Relapse risk is dramatically lower with azithromycin (OR 0.09,95% CI 0.01-0.70) compared to ceftriaxone 1, 2
• Oral administration allows outpatient management for stable patients 1, 2

Avoid Cefixime

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

Geographic Considerations for Resistance Patterns

For cases originating from South Asia: Start azithromycin empirically—fluoroquinolone resistance exceeds 70% in this region 1, 2

For cases with confirmed susceptibility: Fluoroquinolones (ciprofloxacin or ofloxacin) remain effective when susceptibility is confirmed, but the organism must be sensitive to both ciprofloxacin AND nalidixic acid on disc testing 1, 3, 5

Pakistan-specific concern: Ciprofloxacin-resistant and ceftriaxone-resistant typhoid is now common 4

Monitoring and Expected Clinical Response

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

Management of Complications

Intestinal Perforation

• Occurs in 10-15% of patients when illness duration exceeds 2 weeks 2, 3
• Requires immediate surgical intervention with simple excision and closure, successful in up to 88.2% of cases 1, 2

Other Severe Complications

• Gastrointestinal bleeding, typhoid encephalopathy occur in 10-15% of patients with prolonged untreated illness 3
• These complications are more likely if duration of illness exceeds 2 weeks before treatment 3

Critical Pitfalls to Avoid

• Do not discontinue antibiotics prematurely—complete the full 7-14 day course even if fever resolves early 1, 2
• Never use ciprofloxacin empirically for cases from South/Southeast Asia—resistance is nearly universal 1, 2
• Do not rely on ciprofloxacin disc testing alone—the organism must also be sensitive to nalidixic acid to be considered truly fluoroquinolone-sensitive 3
• Avoid cefixime as first-line therapy due to high failure rates of 4-37.6% 1
• Do not use combination typhoid-paratyphoid vaccines—only monovalent S. typhi preparations should be used 1

Specific Dosing Summary

Azithromycin (First-Line)

• Adults: 500 mg once daily for 7-14 days 1, 2
• Children: 20 mg/kg/day (maximum 1g/day) for 7-14 days 1, 2

Ceftriaxone (For Severe Disease)

• Adults: 2g IV daily for 14 days 3
• Children: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1
• Alternative adult dosing: 1-2g IV/IM daily for 5-7 days 1

Ciprofloxacin (Only When Susceptibility Confirmed)

• Use only when both ciprofloxacin and nalidixic acid susceptibility confirmed 3, 5
• FDA-approved for typhoid fever, but resistance patterns limit empiric use 5