Management of Typhoid Fever
Azithromycin is the recommended first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, at a dose of 500 mg once daily for 7-14 days in adults or 20 mg/kg/day (maximum 1g/day) for 7-14 days in children. 1, 2, 3
Treatment Algorithm Based on Severity and Resistance Patterns
Uncomplicated Typhoid Fever
- For uncomplicated cases, oral azithromycin is preferred with superior outcomes, lower risk of clinical failure (OR 0.48), and shorter hospital stays compared to fluoroquinolones 1, 3
- Azithromycin has a lower risk of relapse (OR 0.09) compared to ceftriaxone and is particularly effective against quinolone-resistant strains 3
- Expected fever clearance occurs within 4-5 days of appropriate therapy 1, 2
Severe Typhoid Fever
- For severe cases requiring hospitalization, ceftriaxone 1-2g IV/IM daily for adults or 50-80 mg/kg/day for children (maximum 2g/day) for 5-7 days is recommended 1, 2
- Once clinical improvement occurs with IV therapy, transition to oral azithromycin may be considered 1
- In a study of children with typhoid fever, a flexible-duration of ceftriaxone therapy (until defervescence plus 5 additional days) was effective with no relapses 4
Treatment Based on Resistance Patterns
- For fully susceptible S. typhi strains, fluoroquinolones remain effective, but azithromycin is still a strong alternative 1
- For multidrug-resistant strains, azithromycin or ceftriaxone is recommended 1
- For quinolone-resistant strains (common in South and Southeast Asia), azithromycin is the preferred first-line therapy 1, 3
- Avoid ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 3, 5
Diagnostic Approach
- Blood cultures should be obtained before starting antibiotics when possible, with the highest yield within the first week of symptom onset 1, 2
- Stool and urine cultures become positive after the first week of illness 2
- Do not rely solely on clinical presentation for diagnosis; obtain cultures whenever possible 2
Management of Complications
- Complications of typhoid fever occur in 10-15% of patients and are more likely if duration of illness exceeds 2 weeks 1, 2
- Common complications include gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy 2
- In cases with intestinal perforation, surgical intervention is recommended with simple excision and closure of small perforations 1
- Do not delay surgical intervention in cases with intestinal perforation 1
Monitoring and Follow-up
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1, 3
- Watch for potential drug interactions with azithromycin 1, 3
- Common adverse effects of azithromycin include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 3
- Complete the full course of antibiotics to prevent relapse 1
Prevention
- Typhoid vaccination provides incomplete protection and does not protect against paratyphoid 1, 2, 3
- Vaccination is recommended for travelers to areas where a recognized risk of exposure to typhoid exists 6, 1
- Hand hygiene and appropriate food safety practices are essential preventive measures 1
- Careful selection of food and drink is crucial, as typhoid vaccines are not 100% effective 6
Common Pitfalls to Avoid
- Do not discontinue treatment prematurely; complete the full course of antibiotics to prevent relapse 1
- Do not delay surgical intervention in cases with intestinal perforation 1
- Be aware of increasing resistance to fluoroquinolones, particularly among travelers to South and Southeast Asia 1, 3
- Do not rely on typhoid vaccination as a substitute for careful selection of food and drink 6