What is the recommended treatment for typhoid?

Recommended Treatment for Typhoid Fever

The preferred initial treatment for typhoid fever is intravenous ceftriaxone (2g IV daily for adults) for 14 days, especially for patients with unstable clinical conditions or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1

First-Line Treatment Options

• Intravenous ceftriaxone is the preferred initial treatment for typhoid fever, particularly for patients with severe illness or those from regions with high fluoroquinolone resistance 1
• The typical dosage of ceftriaxone is 2g IV daily for adults, with a recommended treatment duration of 14 days to reduce the risk of relapse 1
• Azithromycin is a suitable oral alternative for uncomplicated disease, especially when fluoroquinolone resistance is confirmed, with resistance to azithromycin currently being rare in many regions 1

Treatment Selection Based on Resistance Patterns

• In regions like South Asia, fluoroquinolones (such as ciprofloxacin) should be avoided as first-line therapy due to high resistance rates exceeding 70% 1
• When testing isolates for antibiotic sensitivity, ciprofloxacin disc testing alone is unreliable; the organism should also be sensitive to nalidixic acid on disc testing to be considered truly sensitive to fluoroquinolones 1
• Azithromycin has shown superior efficacy compared to ofloxacin in populations with both multi-drug resistance (MDR) and nalidixic acid resistance (NaR) in Vietnam 2

Treatment Algorithm Based on Clinical Presentation and Geography

1. Severe illness or patient from South Asia:

   • First choice: Intravenous ceftriaxone 2g daily for 14 days 1
   • Alternative: Azithromycin 20mg/kg/day for 7-14 days 1, 3

2. Uncomplicated illness in regions with low fluoroquinolone resistance:

   • First choice: Ciprofloxacin (when susceptibility is confirmed) 4
   • Alternative: Azithromycin or ceftriaxone 1

3. Uncomplicated illness in regions with high fluoroquinolone resistance:

   • First choice: Azithromycin 20mg/kg/day for 7-14 days 3
   • Alternative: Ceftriaxone or cefixime 5

Comparative Efficacy of Treatment Options

• Azithromycin has demonstrated higher clinical cure rates (85%) compared to ciprofloxacin (62%) and cefixime (71%) in regions with high rates of multidrug-resistant and nalidixic acid-resistant typhoid 3
• The mean fever clearance time is significantly shorter with azithromycin (5.8 days) compared to cefixime (7.1 days) and ciprofloxacin (8.2 days) 3
• Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, though evidence is of low certainty 5

Important Clinical Considerations

• Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients and are more likely if the duration of illness exceeds 2 weeks 1
• Blood cultures have the highest yield within the first week of symptom onset (sensitivity 40-80%), while stool and urine cultures become positive after the first week 1
• Previous vaccination provides incomplete protection against typhoid fever and does not protect against paratyphoid 1

Pitfalls and Caveats

• Fluoroquinolone resistance is increasing globally, particularly in South Asia, making empiric treatment with ciprofloxacin potentially ineffective 1, 6
• Ciprofloxacin is not recommended as a first-line agent in the pediatric population due to an increased incidence of adverse events, including those related to joints and surrounding tissues 4
• The efficacy of ciprofloxacin in eradicating the chronic typhoid carrier state has not been demonstrated 4
• When using cephalosporins, ceftriaxone appears to be more effective than cefixime, which may not perform as well as other treatment options 5