What is the complete prescription for an adult (and child) patient diagnosed with typhoid fever?

Complete Prescription for Typhoid Fever

For uncomplicated typhoid fever, prescribe azithromycin 20 mg/kg/day orally once daily (maximum 1 gram/day) for 5-7 days in both adults and children, as this is the most effective first-line treatment with superior outcomes compared to fluoroquinolones and cephalosporins, particularly in regions with multidrug-resistant and nalidixic acid-resistant strains. 1

Adult Prescription

First-Line Treatment

• Azithromycin 20 mg/kg/day orally once daily (maximum 1 gram/day) for 5-7 days 1
  • This provides the shortest fever clearance time and lowest relapse rates 1
  • Superior to fluoroquinolones in settings with nalidixic acid resistance 2
  • More effective than ceftriaxone for preventing relapse 1

Second-Line Alternatives (if azithromycin unavailable or contraindicated)

• Ciprofloxacin 15 mg/kg orally twice daily (maximum 750 mg twice daily) for 7-10 days 1

  • Use only in areas with documented fluoroquinolone susceptibility 1
  • Less effective in regions with nalidixic acid-resistant strains 3, 2

• Ceftriaxone 80 mg/kg IV once daily (maximum 2-4 grams/day) for 5-7 days 1

  • Reserve for severe cases or treatment failures 1
  • Higher relapse rates compared to azithromycin 1, 4

Pediatric Prescription (≥6 months of age)

First-Line Treatment

• Azithromycin 20 mg/kg/day orally once daily (maximum 1 gram/day) for 5-7 days 1
  • Demonstrated 82% clinical cure rate in children 2
  • Significantly reduces fecal carriage (1.6% vs 19.4% with ofloxacin) 2
  • Well-tolerated with minimal side effects 4, 5

Second-Line Alternatives

• Ciprofloxacin 15 mg/kg orally twice daily for 7-10 days 1

  • Maximum dose: 500 mg every 8 hours or 750 mg every 12 hours 1
  • Avoid in areas with high nalidixic acid resistance 3, 2

• Ceftriaxone 80 mg/kg IV once daily for 5-7 days 1

  • Maximum 2.5 grams/day 4
  • 97% cure rate but higher relapse risk 4

Critical Prescribing Considerations

Resistance Patterns Matter

• In regions with multidrug-resistant (MDR) and nalidixic acid-resistant strains (common in South Asia), azithromycin is superior to fluoroquinolones 3, 2
• Fluoroquinolones show prolonged fever clearance times (8.2 days vs 5.8 days with azithromycin) in resistant strains 2
• 88-93% of isolates in endemic areas demonstrate MDR and nalidixic acid resistance 2

Combination Therapy (Investigational)

• Azithromycin 20 mg/kg/day + cefixime 20 mg/kg/day (divided twice daily, maximum 400 mg twice daily) for 7 days is under investigation for resistant strains 6
• This combination targets both intracellular (azithromycin) and extracellular (cefixime) bacterial populations 6
• Not yet standard of care but may be considered for treatment failures 6

Common Pitfalls to Avoid

Duration Errors

• Do not prescribe shorter than 5 days for azithromycin 1
• Fluoroquinolones require full 7-10 day courses to prevent relapse 1
• Premature discontinuation increases relapse risk significantly 4

Drug Selection Mistakes

• Never use oral live-attenuated Ty21a vaccine during acute infection 7
• Avoid fluoroquinolones as first-line in endemic areas without susceptibility testing 3, 2
• Do not use chloramphenicol, ampicillin, or trimethoprim-sulfamethoxazole in MDR regions 2

Monitoring Requirements

• Assess fever clearance at 5-7 days; persistent fever suggests treatment failure 3, 2
• Mean fever clearance time: 3.65-5.8 days with azithromycin 3, 5
• Follow-up at 4 weeks to detect relapse (occurs in 4-13% of cases) 4, 2

Special Populations

Pregnancy

• Ceftriaxone is preferred during pregnancy 8
• Azithromycin is generally considered safe but use only if clearly needed 8
• Avoid fluoroquinolones due to cartilage toxicity concerns 1

Renal Impairment

• Adjust cefixime dosing when creatinine clearance <60 mL/min 8
• Azithromycin requires no dose adjustment 3

Infants <6 months

• Safety and efficacy not established for cefixime 8
• Use ceftriaxone 50-80 mg/kg IV daily with caution 1

Post-Treatment Considerations

Vaccination After Recovery

• Vaccination is not required after documented typhoid infection 7
• If desired, wait 2-4 weeks after clinical recovery before administering vaccine 7
• Use parenteral Vi polysaccharide vaccine (not oral Ty21a) if recent antibiotic use 7

Carrier State Screening

• Check stool cultures 4 weeks post-treatment to identify chronic carriers 2
• Chronic carriers require prolonged antimicrobial therapy or cholecystectomy 1