Typhoid Fever Treatment
For typhoid fever, intravenous ceftriaxone 2g daily for 14 days is the preferred first-line treatment, particularly for patients with unstable clinical condition or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1
Treatment Algorithm Based on Clinical Presentation and Geographic Origin
Severe or Unstable Disease
- Initiate IV ceftriaxone 2g daily for adults (14-day course) as the definitive first-line therapy 1
- This approach is critical because complications including gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients, especially when illness duration exceeds 2 weeks 1
Uncomplicated Disease with Confirmed or Suspected South Asian Origin
- Avoid fluoroquinolones entirely - more than 70% of isolates from South Asia demonstrate fluoroquinolone resistance 1, 2
- Use azithromycin as the oral alternative - resistance to azithromycin remains rare in most regions 1
- Azithromycin is FDA-approved for typhoid fever treatment 3 and demonstrates excellent efficacy in South Asian populations 4
Uncomplicated Disease from Other Geographic Regions
- Azithromycin remains the preferred oral option given its safety profile and effectiveness 1
- Ciprofloxacin may be considered ONLY if the isolate is sensitive to both ciprofloxacin AND nalidixic acid on disc testing 1
- Critical pitfall: Ciprofloxacin disc testing alone is unreliable - you must confirm nalidixic acid sensitivity to ensure true fluoroquinolone susceptibility 1
Treatment Duration and Monitoring
- Complete the full 14-day course of ceftriaxone to minimize relapse risk 1
- For azithromycin, a 7-day course at 20mg/kg/day (maximum 1g/day) is standard 1
- Blood cultures have highest yield in the first week (40-80% sensitivity), while stool and urine cultures become positive after the first week 1
Key Clinical Caveats
Resistance Patterns
- Extensively drug-resistant typhoid has emerged in Pakistan, requiring careful antimicrobial selection 2
- Ceftriaxone-resistant typhoid is now documented in Pakistan, though ceftriaxone remains effective in most regions 2
- Previous vaccination provides incomplete protection and does NOT protect against paratyphoid 1
Comparative Effectiveness
- Ceftriaxone may result in decreased clinical failure compared to azithromycin, with shorter time to defervescence (0.52 days faster) 5
- Cefixime performs less well than fluoroquinolones when the latter are susceptible, with longer time to defervescence (1.74 days longer) and higher relapse rates 5