Recommended Treatment for Typhoid Fever
Azithromycin is the preferred first-line treatment for typhoid fever, particularly for cases originating from South Asia where fluoroquinolone resistance exceeds 70%, dosed at 500 mg once daily for 7 days in adults or 20 mg/kg/day (maximum 1g/day) for 7 days in children. 1
Treatment Algorithm Based on Geographic Origin and Severity
For Uncomplicated Cases (Outpatient Management)
- Start with azithromycin as empiric therapy for all cases, especially those from South Asia where fluoroquinolone resistance approaches 96% in some regions 1
- Azithromycin demonstrates superior outcomes with lower risk of clinical failure (OR 0.48) compared to fluoroquinolones and significantly shorter hospital stays (approximately 1 day reduction) 1
- The relapse rate with azithromycin is dramatically lower (OR 0.09) compared to ceftriaxone 1
- Dosing: Adults receive 500 mg once daily for 7 days; children receive 20 mg/kg/day (maximum 1g/day) for 7 days 1, 2
For Severe Cases Requiring Hospitalization
- Initiate intravenous ceftriaxone for patients with unstable clinical condition, sepsis features, or inability to tolerate oral medications 3
- Ceftriaxone dosing: 2g IV daily for adults; 50-80 mg/kg/day (maximum 2g/day) IV for children 3, 2
- Treatment duration: 14 days for adults to reduce relapse risk; 5-7 days for children with transition to oral therapy once clinically improved and afebrile for 24 hours 3, 2
- Expect fever clearance within 4-5 days of appropriate therapy 1, 2
Critical Diagnostic Steps Before Treatment
- Obtain blood cultures before starting antibiotics whenever possible, as they have the highest yield (40-80% sensitivity) within the first week of symptom onset 3, 2
- For patients with sepsis features, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures 1
- Bone marrow cultures have higher sensitivity than blood cultures if diagnosis remains uncertain 3
What NOT to Do: Common Pitfalls
- Never use ciprofloxacin empirically for cases from South or Southeast Asia due to resistance rates exceeding 70-96% 1, 2, 4
- Do not rely solely on ciprofloxacin disc testing for susceptibility; the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 3
- Do not discontinue antibiotics prematurely; complete the full 7-day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 1
- Avoid cefixime as first-line therapy due to documented treatment failure rates of 4-37.6% and high relapse rates 1, 5
When Fluoroquinolones Can Be Used
- Fluoroquinolones (ciprofloxacin 500 mg twice daily or ofloxacin) remain effective only when susceptibility is confirmed through appropriate testing 1
- This option is primarily relevant for cases not originating from South Asia and when nalidixic acid sensitivity is documented 3
- The FDA approves ciprofloxacin for typhoid fever caused by Salmonella typhi 6
Monitoring and Expected Clinical Response
- Monitor for clinical improvement; if no response by day 5, consider antimicrobial resistance or alternative diagnosis 1
- Fever should clear within 4-5 days of appropriate therapy 1, 2
- Watch for complications (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) which occur in 10-15% of patients, particularly if illness duration exceeds 2 weeks 3, 2
Alternative Treatment Options
- Cefixime can be used as an alternative oral option at 8 mg/kg/day as a single daily dose for 7-14 days, but requires mandatory test-of-cure at 1 week due to high failure rates 1, 2
- Cefixime may result in increased clinical failure (RR 13.39), microbiological failure (RR 4.07), and relapse (RR 4.45) compared to fluoroquinolones 5
Adverse Effects to Monitor
- Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1
- Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1