What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

First-Line Treatment Recommendation

Azithromycin 500 mg once daily for 7 days is the recommended first-line treatment for typhoid fever, particularly for cases originating from South or Southeast Asia where fluoroquinolone resistance exceeds 70%. 1, 2

Treatment Algorithm Based on Clinical Severity and Geographic Origin

Severe Cases (Sepsis, Encephalopathy, or Septic Shock)

• Start IV ceftriaxone 2g daily immediately after obtaining blood, stool, and urine cultures 2, 3
• Continue for 14 days total to minimize relapse risk (relapse rate <8%) 2, 3
• Transition to oral therapy when clinically improved 1
• Consider adding corticosteroids in severe typhoid fever 2

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

• Azithromycin 500 mg once daily for 7-14 days is preferred 1, 2
• Azithromycin demonstrates superior efficacy with lower clinical failure (OR 0.48) and dramatically lower relapse rates (OR 0.09) compared to ceftriaxone 1
• Alternative: Oral cefixime or IV ceftriaxone if azithromycin unavailable 1, 2

Uncomplicated Cases from Other Regions (If Susceptibility Confirmed)

• Fluoroquinolones (ciprofloxacin 500 mg twice daily or ofloxacin) for 7 days if organism is susceptible to both ciprofloxacin AND nalidixic acid on disc testing 1, 3, 4
• Critical caveat: Ciprofloxacin disc testing alone is unreliable; the organism must also be sensitive to nalidixic acid to be considered truly fluoroquinolone-sensitive 3
• Fever clearance typically occurs within 4 days with cure rates >96% 2
• Alternative older agents (if fully susceptible): chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole 1

Pediatric Considerations

• Children <3 months: Use third-generation cephalosporin 2
• Children 1-17 years: Azithromycin or ceftriaxone based on severity and resistance patterns 2
• Note that fluoroquinolones carry increased risk of joint-related adverse events in pediatric populations 4

Treatment Duration and Monitoring

• Continue treatment for 14 days regardless of agent chosen to reduce relapse risk 2, 3
• Expected fever clearance: 4-5 days with appropriate therapy 1, 2
• Monitor for complications (intestinal perforation, GI bleeding, encephalopathy) which occur in 10-15% of patients, particularly if illness duration exceeds 2 weeks 2, 3
• Common adverse effects of azithromycin include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1

Critical Pitfalls to Avoid

• Never use ciprofloxacin empirically for cases originating from South Asia due to resistance rates exceeding 70% 1, 3, 5
• Do not rely on ciprofloxacin disc testing alone; verify nalidixic acid susceptibility 3
• Avoid shorter treatment courses (<14 days) as this increases relapse risk 2, 3
• Previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid fever 1, 3
• Extensively drug-resistant strains have emerged in Pakistan, requiring careful consideration of local resistance patterns 5, 6

Diagnostic Confirmation

• Blood culture remains the gold standard (sensitivity 40-80% in first week) with 2-3 specimens of 20 mL each in adults drawn prior to antibiotics 2
• Bone marrow culture is more sensitive, especially if antibiotics already administered 2
• Larger blood volumes are needed due to low bacteremia (0.3 CFU/mL) 2