Typhoid Fever Treatment: Recommended Drugs, Doses, and Frequencies
Azithromycin is the first-line therapy for typhoid fever due to its lower risk of clinical failure, shorter hospital stay, and lower risk of relapse compared to other antibiotics. 1
First-Line Treatment Options
For Fully Sensitive Strains
- Azithromycin
- Adult dose: 500-1000 mg orally once daily for 7 days
- Pediatric dose: 10-20 mg/kg orally once daily for 7 days (maximum 1000 mg/day)
For Quinolone-Resistant Strains
- Azithromycin (same dosing as above)
- Ceftriaxone (alternative)
For Multidrug-Resistant Strains
- Ceftriaxone or Cefixime
- Cefixime: 15-20 mg/kg/day orally divided twice daily (maximum 400 mg/dose) for 7-14 days
- Ceftriaxone: As above 1
Alternative Treatment Options
Fluoroquinolones (for fully sensitive strains)
- Ciprofloxacin
- Adult dose: 500 mg orally every 12 hours for 10 days
- Pediatric dose: 10 mg/kg orally every 12 hours (maximum 500 mg/dose) for 10 days 3
Other Alternatives
- Chloramphenicol: 50-75 mg/kg/day divided into 4 doses for 14 days (continue for 8-10 days after fever resolution) 1, 4
- Amoxicillin: 75-100 mg/kg/day divided into 3 doses for 14 days
- Trimethoprim-sulfamethoxazole: 8-10 mg/kg/day (trimethoprim component) divided into 2 doses for 14 days 1
Treatment Duration
- Azithromycin: 7 days
- Ciprofloxacin: 10 days
- Ceftriaxone: 10-14 days
- Chloramphenicol: 14 days (continue for 8-10 days after fever resolution) 1
Important Clinical Considerations
Resistance Patterns
- Fluoroquinolone resistance is common in South and Southeast Asia, with resistance to nalidixic acid (a marker for decreased ciprofloxacin susceptibility) increasing from 19% in 1999 to 59% in 2008 1
- Extensively drug-resistant strains have emerged in Pakistan 5
- In some areas, susceptibility to older first-line antimicrobials like chloramphenicol has re-emerged 5
Special Populations
- Pregnant women: Azithromycin is preferred due to its safety profile 1
- Children: Azithromycin is preferred over fluoroquinolones 1
- Renal impairment: Dose adjustments required for ciprofloxacin:
- CrCl 30-50 mL/min: 250-500 mg every 12 hours
- CrCl 5-29 mL/min: 250-500 mg every 18 hours
- Hemodialysis/peritoneal dialysis: 250-500 mg every 24 hours (after dialysis) 3
Treatment Monitoring
- Monitor fever clearance time (typically 3-5 days with effective therapy)
- Ensure clinical improvement within 48-72 hours of initiating appropriate therapy 1
- Blood cultures should become negative early in treatment (significantly faster with ceftriaxone compared to chloramphenicol) 4
Treatment Pitfalls to Avoid
- Inadequate treatment duration increases the risk of relapse 1
- Antimotility agents should be avoided in suspected typhoid fever 1
- Underestimating resistance patterns - always consider local resistance patterns when selecting therapy
- Ciprofloxacin treatment failure - despite in vitro susceptibility, clinical failure with ciprofloxacin has been reported; consider ceftriaxone as an effective alternative 6
- Delayed administration of antibiotics - treatment should begin as soon as typhoid fever is suspected in high-risk patients
Comparative Effectiveness
- Azithromycin shows lower risk of clinical failure (OR 0.48; 95% CI, 0.26-0.89), shorter hospital stay (-1.04 days; 95% CI, -1.73 to -0.34 days), and lower risk of relapse (OR 0.09; 95% CI, 0.01-0.70) compared to other antibiotics 1
- Ceftriaxone leads to faster blood culture clearance compared to chloramphenicol (0% vs 60% positive cultures on day 3 of treatment) 4
- Cefixime may be less effective than fluoroquinolones for treatment of typhoid fever (RR for clinical failure 13.39,95% CI 3.24 to 55.39) 5
Remember that local resistance patterns should guide therapy selection, and treatment should be adjusted based on antimicrobial susceptibility testing when available.