What is the recommended treatment for typhoid?

Treatment of Typhoid Fever

First-Line Antibiotic Selection

For typhoid fever, intravenous ceftriaxone 2g daily for 14 days is the preferred first-line treatment, especially for patients with unstable clinical condition or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1

Treatment Algorithm Based on Geographic Origin and Resistance Patterns

For patients from South Asia:

• Avoid fluoroquinolones as first-line therapy due to resistance rates exceeding 70% in isolates imported from this region 1
• Use ceftriaxone 2g IV daily for adults (or 75 mg/kg/day for children, maximum 2g/day) for 14 days to reduce relapse risk 1, 2
• The 14-day duration is critical—shorter courses (5-8 days) have shown efficacy but the extended duration minimizes relapse 2, 3

For uncomplicated disease with confirmed susceptibility:

• Azithromycin is a suitable oral alternative when fluoroquinolone resistance is confirmed, as azithromycin resistance remains rare in most regions 4, 1
• Azithromycin demonstrated lower clinical failure rates (OR 0.48,95% CI 0.26-0.89) and shorter hospital stays compared to fluoroquinolones 4
• Azithromycin also showed lower relapse rates (OR 0.09,95% CI 0.01-0.70) compared to ceftriaxone 4

For fully sensitive isolates (rare):

• Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi 5
• Critical caveat: Ciprofloxacin disc testing alone is unreliable—the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1
• Given widespread resistance, fluoroquinolones should only be used when both ciprofloxacin AND nalidixic acid sensitivity are confirmed 1

Dosing Specifics

Ceftriaxone:

• Adults: 2g IV daily for 14 days 1
• Children: 75 mg/kg/day IV (maximum 2g/day) in two divided doses until defervescence, then continue 5 additional days 2
• Mean defervescence time is 4-5 days 2, 6

Azithromycin:

• Preferred oral option for uncomplicated disease with confirmed or suspected fluoroquinolone resistance 4, 1

Ciprofloxacin (only if fully sensitive):

• FDA-approved for typhoid fever, but efficacy in eradicating chronic carrier state not demonstrated 5

Critical Clinical Considerations

Complications occur in 10-15% of patients and are more likely if illness duration exceeds 2 weeks before treatment: 1

• Gastrointestinal bleeding
• Intestinal perforation
• Typhoid encephalopathy

Diagnostic approach:

• Blood cultures have highest yield (40-80% sensitivity) within the first week of symptoms 1
• Bone marrow cultures have higher sensitivity than blood cultures 1
• Avoid the Widal serological test—it lacks sensitivity and specificity 1

Common Pitfalls to Avoid

Do not rely on ciprofloxacin disc testing alone—nalidixic acid sensitivity must also be confirmed to ensure true fluoroquinolone susceptibility 1

Do not use shorter ceftriaxone courses without careful follow-up—while 5-8 day courses show efficacy, the 14-day regimen reduces relapse risk 1, 2, 3

Do not assume vaccination provides complete protection—previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid 1

Initiate empiric therapy before culture results in clinically suspected cases, then adjust based on susceptibility testing 5