What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

For typhoid fever, fluoroquinolones are the first-line treatment for fully sensitive strains, while azithromycin or ceftriaxone should be used for multidrug-resistant or quinolone-resistant strains. 1

Treatment Algorithm Based on Resistance Patterns

First-Line Treatment Options:

1. For fully sensitive Salmonella typhi:

   • Fluoroquinolones (ciprofloxacin or ofloxacin) 1
   • Alternative (if fluoroquinolones unavailable or contraindicated): chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole

2. For multidrug-resistant strains:

   • Fluoroquinolones or cefixime 1
   • Alternative: azithromycin

3. For quinolone-resistant strains:

   • Azithromycin or ceftriaxone 1
   • Alternative: cefixime

Dosing Recommendations

• Ciprofloxacin: 500 mg orally twice daily for 7 days 2
• Azithromycin: 20 mg/kg/day (maximum 1000 mg/day) for 5-7 days 3
• Ceftriaxone: 75 mg/kg/day (maximum 2.5 g/day) for 5-7 days 3

Special Considerations

Resistance Patterns

Increasing resistance to fluoroquinolones has been observed, particularly among travelers to South and Southeast Asia 1. Nalidixic acid resistance, a marker for decreased susceptibility to ciprofloxacin, increased from 19% in 1999 to 59% in 2008 1.

Clinical Efficacy

• Fluoroquinolones have shown excellent efficacy with average fever clearance time of less than 4 days and cure rates >96% for sensitive strains 1
• Azithromycin demonstrated 94% cure rates in children and adolescents with uncomplicated typhoid fever 3
• Ceftriaxone has shown 97% efficacy but may have higher relapse rates compared to azithromycin 3

Treatment Duration

• Standard treatment course is 7-14 days depending on the antibiotic used
• To reduce risk of relapse, treatment should be continued for 14 days for severe cases 1

Complications and Management

Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients, especially if illness duration exceeds 2 weeks 1. These complications require aggressive management and may necessitate surgical intervention for intestinal perforation.

Common Pitfalls to Avoid

1. Ignoring resistance patterns: Always consider local resistance patterns when selecting antibiotics. In many regions, particularly South Asia, resistance to fluoroquinolones is common.

2. Relying on vaccination status: Typhoid vaccination provides incomplete protection and does not protect against paratyphoid fever 1.

3. Delayed treatment: Early treatment leads to better outcomes. Intestinal perforation and death were more common in patients treated later in their clinical course 1.

4. Inadequate dosing: Low doses of appropriate antimicrobial therapy result in longer fever clearance times and higher case fatality ratios 1.

5. Overlooking concomitant infections: Patients returning from endemic areas may have multiple infections simultaneously.

In summary, the choice of antibiotic for typhoid fever should be guided by local resistance patterns, with fluoroquinolones remaining the first choice for fully sensitive strains, and azithromycin or ceftriaxone for resistant strains. Early and appropriate treatment significantly reduces morbidity and mortality.