What is the recommended therapy for typhoid fever?

Recommended Therapy for Typhoid Fever

Azithromycin 500 mg once daily for 7 days (or 20 mg/kg/day in children, maximum 1g/day) is the preferred first-line treatment for typhoid fever, particularly given the widespread fluoroquinolone resistance exceeding 70% in South Asia where most cases originate. 1, 2

Treatment Algorithm Based on Clinical Severity and Geographic Origin

For Uncomplicated Cases (Outpatient Management)

• Start azithromycin immediately as empiric therapy without waiting for culture results, especially for cases from South Asia 1, 2
• Azithromycin demonstrates superior outcomes with significantly lower clinical failure rates (OR 0.48) compared to fluoroquinolones and dramatically lower relapse rates (OR 0.09) compared to ceftriaxone 1, 2
• The drug also reduces hospital stay by approximately 1 day compared to fluoroquinolones 1
• Dosing: 500 mg once daily for 7 days in adults; 20 mg/kg/day (maximum 1g/day) for 7 days in children 1, 2

For Severe Cases Requiring Hospitalization

• Initiate ceftriaxone 2g IV daily for adults or 50-80 mg/kg/day (maximum 2g/day) IV for children for 5-7 days 3, 2
• Continue IV therapy until the patient is clinically improved and afebrile for 24 hours, then transition to oral azithromycin to complete treatment 2
• The total treatment duration should be 14 days to minimize relapse risk 3

Critical Geographic Considerations

Avoid Ciprofloxacin in Most Cases

• Never use ciprofloxacin empirically for cases originating from South or Southeast Asia where resistance rates approach 96% in some regions 1, 2
• Ciprofloxacin may only be considered when susceptibility is confirmed AND the isolate is sensitive to nalidixic acid on disc testing (ciprofloxacin disc testing alone is unreliable) 3
• Even the FDA label lists typhoid fever as an indication for ciprofloxacin, but this predates current resistance patterns 4

Why Azithromycin Over Cefixime

• Cefixime has documented treatment failure rates of 4-37.6% in clinical practice 1
• If cefixime must be used (8 mg/kg/day as single daily dose for 7-14 days), a mandatory test-of-cure at 1 week is required due to high failure rates 1, 2
• The WHO lists cefixime only as an "alternative" option, not first-line 1

Diagnostic Approach 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—do not delay treatment 1
• Bone marrow cultures have higher sensitivity than blood cultures but are rarely practical 3
• Avoid the Widal test as it lacks 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 antibiotic resistance or an alternative diagnosis 1
• Complete the full 7-day course even if fever resolves early, as premature discontinuation leads to relapse in 10-15% of cases 1

Management of Complications

• Complications (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) occur in 10-15% of patients, particularly when illness duration exceeds 2 weeks 3, 2
• Intestinal perforation requires surgical intervention with simple excision and closure, successful in up to 88.2% of cases 1

Common Pitfalls to Avoid

• Do not rely on clinical presentation alone—obtain cultures whenever possible as symptoms can be altered by previous antimicrobial use 2, 5
• Do not discontinue antibiotics prematurely even if fever resolves early; incomplete treatment increases relapse risk 1
• Do not assume vaccination provides complete protection—previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid 3, 2

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

Prevention for Future Exposure

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa), though it provides incomplete protection 1, 3
• Hand hygiene and appropriate food/water safety precautions remain essential even after vaccination 3, 2