What is the recommended management for typhoid fever?

Typhoid Fever Management

Immediate Treatment Approach

For suspected typhoid fever, start azithromycin 500 mg once daily for 7-14 days as first-line therapy, particularly for cases from South/Southeast Asia where fluoroquinolone resistance is high; for severe cases with sepsis or encephalopathy, initiate IV ceftriaxone immediately after obtaining cultures. 1, 2

Diagnostic Strategy

Obtain blood cultures before starting antibiotics - this is the gold standard with highest yield (40-80% sensitivity) in the first week of symptoms. 1

• Draw 2-3 specimens of 20 mL each (adults) prior to antibiotics, as bacteremia levels are low (0.3 CFU/mL). 1
• Bone marrow culture is more sensitive than blood, especially if antibiotics have already been given, though more invasive. 1
• Add stool and urine cultures as adjuncts, particularly after the first week when they become positive. 1, 3

Treatment Algorithm by Severity and Geography

Severe Cases (Sepsis, Fever ≥38.5°C, Shock, Encephalopathy)

Start IV ceftriaxone 50-80 mg/kg/day (maximum 2g/day) immediately after obtaining cultures. 1, 3

• Transition to oral therapy (azithromycin or cefixime) once clinically improved and afebrile for 24 hours. 3
• Relapse rate with ceftriaxone is <8%. 1
• Consider adding steroids in severe typhoid fever. 1

Uncomplicated Cases from South/Southeast Asia (High Fluoroquinolone Resistance)

Azithromycin 500 mg once daily (or 20 mg/kg/day, maximum 1g/day in children) for 7-14 days is first-line. 1, 2, 3

• Superior efficacy with lower clinical failure (OR 0.48) and relapse rates (OR 0.09) compared to fluoroquinolones and ceftriaxone. 2, 3, 4
• Cure rate of 94% in children. 3
• Shorter hospital stays compared to fluoroquinolones. 2
• Do NOT use ciprofloxacin empirically for cases from South Asia due to high resistance rates. 2, 3, 5

Cases from Other Regions (If Susceptibility Confirmed)

Fluoroquinolones (ciprofloxacin 500-750 mg twice daily or ofloxacin) can be used if susceptibility is confirmed. 1, 6, 7

• Fever clearance <4 days with cure rates >96%. 1
• Ciprofloxacin is FDA-approved for typhoid fever (enteric fever) caused by Salmonella typhi. 6
• However, increasing resistance has been observed, particularly from travelers to South and Southeast Asia. 2

Alternative for Fully Susceptible Strains

For fully susceptible S. typhi, alternatives include chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole, though resistance to these agents is significantly high in many regions. 2, 8

Treatment Duration and Monitoring

Continue treatment for 14 days to reduce relapse risk. 1

• Expected fever clearance is 4-5 days with appropriate therapy. 1, 2, 3
• If fever persists beyond 5 days, consider treatment failure and reassess antibiotic choice based on culture sensitivities. 1
• Monitor for complications including intestinal perforation, GI bleeding, and encephalopathy, which occur in 10-15% of patients. 1, 3

Pediatric Considerations

• For children <3 months, use third-generation cephalosporin. 1
• For complicated UTI and pyelonephritis in children 1-17 years: azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days or cefixime 8 mg/kg/day for 7-14 days. 3
• Note: Ciprofloxacin is not first-choice in pediatrics due to increased incidence of joint-related adverse events. 6

Common Pitfalls to Avoid

• Do not use ciprofloxacin empirically for cases originating from South Asia - resistance rates are extremely high. 2, 3
• Do not rely solely on clinical presentation for diagnosis; obtain cultures whenever possible. 3
• Avoid indiscriminate antibiotic use without sensitivity testing, as this promotes resistance. 8
• Remember that typhoid vaccination provides incomplete protection and does not protect against paratyphoid. 2, 3

Expected Adverse Effects

Azithromycin commonly causes GI symptoms: nausea, vomiting, abdominal pain, and diarrhea. 2 Monitor for potential drug interactions with azithromycin. 2