Typhoid Fever Treatment
First-Line Recommendation
For typhoid fever, initiate intravenous ceftriaxone 2g daily for 14 days as the preferred first-line treatment, especially for patients with unstable clinical condition or those with exposure to South Asia where fluoroquinolone resistance exceeds 70%. 1
Treatment Algorithm Based on Clinical Presentation and Geographic Origin
Severe or Hospitalized Patients
- Intravenous ceftriaxone 2g daily for 14 days is the preferred regimen for adults with unstable clinical condition 1
- The 14-day duration is critical to reduce relapse risk 1
- This approach is particularly important for infections acquired in Asia where fluoroquinolone resistance is widespread 1
Uncomplicated Disease (Stable Outpatients)
- Azithromycin is a suitable oral alternative when fluoroquinolone resistance is confirmed, as azithromycin resistance remains rare in most regions 1
- Oral therapy is appropriate only for clinically stable patients without complications 1
Geographic Considerations and Resistance Patterns
South Asian Origin (India, Pakistan, Bangladesh)
- Avoid fluoroquinolones as first-line therapy due to resistance rates exceeding 70% in isolates imported from these regions 1
- Even when ciprofloxacin disc testing shows sensitivity, the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1
- Ciprofloxacin disc testing alone is unreliable 1
When Fluoroquinolones May Be Considered
- Ciprofloxacin is FDA-approved for typhoid fever 2
- However, clinical use should be restricted to confirmed susceptible isolates from regions without high fluoroquinolone resistance 1, 3
- Recent evidence shows azithromycin and newer fluoroquinolones like gatifloxacin perform equally well in some settings 3
Critical Timing and Complications
Duration of Illness Matters
- Complications occur in 10-15% of patients including gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy 1
- These complications are more likely if illness duration exceeds 2 weeks before treatment 1
- This underscores the importance of early diagnosis and prompt treatment initiation
Diagnostic Approach
- Blood cultures have highest yield (40-80% sensitivity) within the first week of symptom onset 1
- Bone marrow cultures have higher sensitivity than blood cultures 1
- Do not rely on Widal serological testing as it lacks adequate sensitivity and specificity 1
Common Pitfalls to Avoid
Fluoroquinolone Misuse
- Never assume fluoroquinolone susceptibility based on ciprofloxacin disc testing alone without confirming nalidixic acid sensitivity 1
- Fluoroquinolone resistance is now the norm in South Asia, not the exception 1, 3
Inadequate Treatment Duration
- Shorter courses increase relapse risk 1
- The full 14-day course of ceftriaxone is necessary even if clinical improvement occurs earlier 1
Vaccination Misconceptions
- Previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid 1
- Vaccination status should not delay empiric treatment in suspected cases 1
Alternative Regimens Based on Evidence Quality
Ceftriaxone vs Azithromycin
- Both agents show excellent efficacy and safety profiles 3
- Ceftriaxone may result in decreased clinical failure compared to azithromycin, though evidence is limited to small trials 4
- Time to defervescence may be 0.52 days shorter with ceftriaxone compared to azithromycin 4