Typhoid Fever Treatment
For typhoid fever, use intravenous ceftriaxone 2g daily for 14 days as first-line therapy, particularly for patients with unstable clinical condition or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1
First-Line Treatment Selection
Ceftriaxone is the preferred initial agent for most cases of typhoid fever in the current era of widespread fluoroquinolone resistance 1. The standard regimen is:
Azithromycin is the preferred oral alternative for uncomplicated disease, especially when fluoroquinolone resistance is confirmed 1. Research demonstrates azithromycin achieves:
- Clinical cure rates of 82-85% 2, 3
- Shorter fever clearance times (5.8 days) compared to fluoroquinolones (8.2 days) 3
- Lower post-treatment fecal carriage rates (1.6%) versus fluoroquinolones (19.4%) 3
Critical Geographic Considerations
Avoid fluoroquinolones as first-line therapy in South Asian cases due to resistance rates exceeding 70% 1. This includes:
- India, Pakistan, Bangladesh, Nepal 1
- Over 93% of isolates from these regions show nalidixic acid resistance 2, 3
If considering ciprofloxacin (only for non-South Asian cases with confirmed susceptibility), the organism must be sensitive to both ciprofloxacin AND nalidixic acid on disc testing—ciprofloxacin disc testing alone is unreliable 1. The FDA-approved dosing for typhoid is per standard ciprofloxacin protocols 4.
Treatment Duration and Monitoring
Complete the full 14-day course to minimize relapse risk 1. Key monitoring points:
- Complications (GI bleeding, perforation, encephalopathy) occur in 10-15% of patients, particularly if illness duration exceeds 2 weeks before treatment 1
- Blood cultures have highest yield (40-80% sensitivity) in the first week 1
- Bone marrow cultures have higher sensitivity than blood cultures if diagnosis remains uncertain 1
Common Pitfalls to Avoid
Do not rely on previous vaccination status to exclude typhoid—vaccination provides incomplete protection and does not protect against paratyphoid 1.
Do not use the Widal serological test—it lacks adequate sensitivity and specificity and is not recommended 1.
Do not assume fluoroquinolone susceptibility based on geographic origin alone—resistance patterns must guide therapy, with South Asian isolates having particularly high resistance rates 1, 5.