Treatment of Typhoid Fever
First-Line Recommendation
Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for typhoid fever in adults, particularly for cases originating from South Asia where fluoroquinolone resistance exceeds 70%. 1, 2
Treatment Algorithm Based on Geographic Origin and Resistance
For Cases from South/Southeast Asia (High Fluoroquinolone Resistance)
- Start with azithromycin empirically - resistance rates to ciprofloxacin approach 96% in some South Asian regions, making fluoroquinolones unreliable 1, 2
- Azithromycin demonstrates superior outcomes with lower risk of clinical failure (OR 0.48) and significantly shorter hospital stays compared to fluoroquinolones 1, 2
- Risk of relapse is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 2
For Severe or Unstable Patients
- Initiate IV ceftriaxone 2g daily for adults when patients present with sepsis features or severe illness 3
- Transition to oral therapy once clinical improvement occurs 2
- Complete a full 14-day course to minimize relapse risk 3
For Confirmed Susceptible Strains
- Fluoroquinolones (ciprofloxacin or ofloxacin) remain effective when susceptibility is documented 1, 4
- Critical caveat: Ciprofloxacin disc testing alone is unreliable - the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 3
Specific Dosing Regimens
Azithromycin
Ceftriaxone
- Adults: 1-2g IV/IM daily for 5-7 days (or 2g daily for 14 days in severe cases) 1, 3
- Children: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1
Ciprofloxacin (only if susceptibility confirmed)
Diagnostic Approach Before Treatment
- Obtain blood cultures immediately before starting antibiotics - highest yield within the first week of symptom onset (sensitivity 40-80%) 3
- For patients with sepsis features, start broad-spectrum therapy immediately after collecting blood, stool, and urine cultures 1, 2
- Bone marrow cultures have higher sensitivity than blood cultures if diagnosis remains uncertain 3
- Avoid the Widal test - it lacks adequate sensitivity and specificity 3
Monitoring and Expected Clinical Response
- Expect fever clearance within 4-5 days of appropriate therapy 1, 2
- If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 1
- Complete the full 7-day course minimum even if fever resolves early - premature discontinuation increases relapse risk (10-15% with inadequate treatment) 1
Critical Pitfalls to Avoid
- Never use ciprofloxacin empirically for cases from South or Southeast Asia - resistance rates are prohibitively high 1, 2
- Do not rely on ciprofloxacin disc testing alone without confirming nalidixic acid sensitivity 3
- Do not discontinue antibiotics when fever resolves - complete the full course to prevent relapse 1
- Avoid combination typhoid-paratyphoid vaccines; only monovalent S. typhi preparations should be used 1
Management of Complications
- Intestinal perforation occurs in 10-15% of patients with illness duration exceeding 2 weeks 1, 3
- Surgical intervention with simple excision and closure is required, with success rates up to 88.2% 1
- Other complications include gastrointestinal bleeding and typhoid encephalopathy, more likely after 2 weeks of illness 3
Adverse Effects and Drug Interactions
- Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 2
- Monitor for QT-prolonging medication interactions with azithromycin 1, 2
Prevention Considerations
- Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) 5, 3
- Vaccination provides incomplete protection (51-76% for inactivated vaccine, 67% for oral vaccine) and does not protect against paratyphoid 5, 2, 3
- Food and water safety precautions remain essential even after vaccination 5, 3
- Booster doses of inactivated vaccine should be given every 3 years for continued exposure 5