What is the appropriate prescription format for an adult with uncomplicated typhoid fever, assuming no drug allergies, normal renal and hepatic function, and no contraindications?

Prescription for Typhoid Fever in Adults

For uncomplicated typhoid fever in adults, prescribe azithromycin 500 mg orally once daily for 7-14 days as first-line therapy. 1, 2, 3

First-Line Treatment: Azithromycin

Prescription format:

• Drug: Azithromycin 500 mg tablets
• Dose: 500 mg orally once daily
• Duration: 7-14 days (complete full course)
• Instructions: Take with or without food; complete entire course even if fever resolves early 1, 2, 3

Why Azithromycin is Preferred

• Azithromycin reduces clinical failure by 52% compared to fluoroquinolones (OR 0.48) 1, 2, 3
• Hospital stays are approximately 1 day shorter than with fluoroquinolones 1, 2
• Relapse risk is 91% lower than with ceftriaxone (OR 0.09) 1, 2, 3
• Remains effective against multidrug-resistant strains (resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole) 1, 3
• Safe in pregnancy (FDA Category B) 3

Geographic Resistance Considerations

• Do NOT use ciprofloxacin empirically for cases from South or Southeast Asia—fluoroquinolone resistance exceeds 70% in these regions, approaching 96% in some areas 1, 2, 3, 4
• Ciprofloxacin may only be considered when culture confirms nalidixic acid susceptibility AND the case is not from South/Southeast Asia 2, 3

Second-Line Treatment: Ceftriaxone

When azithromycin is unavailable or contraindicated:

• Drug: Ceftriaxone
• Dose: 2-4 g IV once daily (adults) 1
• Duration: 5-7 days 1, 3
• Note: Ceftriaxone has higher relapse rates than azithromycin (OR 11.1) but maintains efficacy against multidrug-resistant strains 1, 2

Alternative Oral Option (Third-Line): Ciprofloxacin

Only when susceptibility is laboratory-confirmed:

• Drug: Ciprofloxacin 500 mg tablets 5
• Dose: 500 mg orally every 12 hours 5
• Duration: 10 days 5
• Critical requirement: Use ONLY if culture shows nalidixic acid susceptibility AND case is not from South/Southeast Asia 2, 3

Diagnostic Considerations Before Prescribing

• Obtain blood cultures before starting antibiotics whenever possible—highest yield in first week of illness (sensitivity 40-80%) 2, 3
• In patients with sepsis features, start empiric therapy immediately after collecting blood cultures 2, 3

Expected Clinical Response

• Fever should clear within 4-5 days of appropriate therapy 1, 2, 3
• If no improvement by day 5, consider resistance or alternative diagnosis 2
• Mean fever clearance time with azithromycin: 5.8 days (95% CI 5.1-6.5) 3

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely—complete the full 7-14 day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 1, 2, 3
• Never use cefixime as first-line—treatment failure rates of 4-37.6% and 13-fold higher risk of clinical failure compared to fluoroquinolones 2, 3
• Never rely on Widal test for diagnosis—inadequate sensitivity and specificity 2, 6
• Avoid empiric ciprofloxacin for travel-associated cases from endemic regions due to widespread resistance 1, 2, 3, 4

Monitoring and Follow-Up

• Monitor for common azithromycin adverse effects: nausea, vomiting, abdominal pain, diarrhea 2, 3
• Check for QT-prolonging drug interactions before prescribing azithromycin 2, 3
• Watch for complications if illness duration exceeds 2 weeks—intestinal perforation occurs in 10-15% of such cases 2, 3

Special Populations

Pregnant patients:

• Azithromycin is safe (FDA Category B) 3
• Fluoroquinolones are contraindicated in pregnancy 3
• Ceftriaxone is also safe in pregnancy 1

Patients with renal impairment (if using ciprofloxacin):

• CrCl 30-50 mL/min: 250-500 mg every 12 hours 5
• CrCl 5-29 mL/min: 250-500 mg every 18 hours 5
• Hemodialysis: 250-500 mg every 24 hours (after dialysis) 5