What is the recommended treatment for typhoid?

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 returning from Asia where fluoroquinolone resistance exceeds 70%. 1

Treatment Algorithm Based on Clinical Presentation and Geography

Severe or Unstable Disease

• Intravenous ceftriaxone 2g daily for 14 days is the treatment of choice for adults with severe presentation or hemodynamic instability 1
• The 14-day duration is critical to reduce relapse risk 1
• This approach is particularly important given that complications (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) occur in 10-15% of patients, especially when illness duration exceeds 2 weeks 1

Uncomplicated Disease with Known Geographic Origin

For patients from South Asia (India, Pakistan, Bangladesh, Nepal):

• Avoid fluoroquinolones as first-line therapy due to resistance rates exceeding 70% in isolates imported from these regions 1
• Azithromycin is the preferred oral alternative for uncomplicated disease, as resistance to azithromycin remains rare in many regions 1
• Ceftriaxone remains effective even in these high-resistance areas 1

For patients from other endemic regions with lower fluoroquinolone resistance:

• Fluoroquinolones may still be considered, but only after confirming susceptibility 1, 2
• The organism must be sensitive to both ciprofloxacin AND nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1
• Ciprofloxacin disc testing alone is unreliable 1

FDA-Approved Options

• Ciprofloxacin is FDA-approved for typhoid fever (enteric fever) caused by Salmonella typhi 3
• However, the FDA label notes that ciprofloxacin efficacy in eradicating the chronic typhoid carrier state has not been demonstrated 3

Critical Resistance Considerations

The resistance landscape has fundamentally changed treatment paradigms:

• In South Asia, more than 70% of isolates show fluoroquinolone resistance 1
• Ciprofloxacin-resistant and ceftriaxone-resistant typhoid is now common in Pakistan 2
• Testing for nalidixic acid sensitivity is mandatory before considering any fluoroquinolone therapy, as ciprofloxacin disc testing alone misses resistance 1

Alternative Regimens

Azithromycin

• Suitable for uncomplicated disease when fluoroquinolone resistance is confirmed 1
• Research supports 7-day courses at 20mg/kg/day (maximum 1g/day) with excellent efficacy 4, 5
• Shorter 5-day courses have shown effectiveness in children and adolescents 5

Newer Fluoroquinolones

• Gatifloxacin has shown effectiveness in regions where older fluoroquinolones (ciprofloxacin, ofloxacin) have failed due to nalidixic acid resistance 4, 6
• In Vietnam (2004-05), gatifloxacin performed as well as azithromycin despite high resistance rates 4

Diagnostic Timing and Culture Guidance

Obtain cultures before initiating therapy:

• 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
• Stool and urine cultures become positive after the first week (sensitivities 35-65% and 0-58% respectively) 1
• Do not use the Widal serological test as it lacks sensitivity and specificity 1

Common Pitfalls to Avoid

• Never rely on ciprofloxacin disc testing alone without nalidixic acid sensitivity testing 1
• Do not assume prior typhoid vaccination provides protection against current infection, as it provides incomplete protection and does not protect against paratyphoid 1
• Avoid fluoroquinolones empirically in patients from South Asia without confirmed susceptibility 1
• Do not use shorter treatment courses than recommended, as the 14-day duration for ceftriaxone specifically reduces relapse risk 1