What is the recommended treatment for typhoid fever?

Management of Typhoid Fever

First-Line Treatment Recommendation

Azithromycin is the preferred first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, at a dose of 500 mg once daily for 7 days in adults or 20 mg/kg/day (maximum 1g/day) for 7 days in children. 1, 2, 3

Treatment Algorithm Based on Resistance Patterns

For Quinolone-Resistant or Unknown Susceptibility Strains

• Start with azithromycin as empiric therapy, especially for cases originating from South Asia where fluoroquinolone resistance exceeds 70% 1, 2, 4
• Azithromycin demonstrates superior outcomes with lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones 1, 3
• Risk of relapse is significantly lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 3

For Fully Susceptible Strains

• Fluoroquinolones (ciprofloxacin or ofloxacin) remain effective when susceptibility is confirmed 1, 3, 5
• However, avoid empiric ciprofloxacin use for cases from South Asia due to resistance rates approaching 96% in some regions 6, 3, 7

For Severe Cases Requiring Parenteral Therapy

• Ceftriaxone 1-2g IV/IM daily for adults or 50-80 mg/kg/day (maximum 2g/day) for children for 5-7 days 1, 2, 3
• Transition to oral azithromycin once clinical improvement occurs and temperature has been normal for 24 hours 1, 2

Specific Dosing Guidelines

Adults

• Azithromycin: 500 mg once daily for 7-14 days 1, 3
• Ceftriaxone: 1-2g IV/IM daily for 5-7 days 1
• Ciprofloxacin (if susceptible): 500 mg twice daily per FDA labeling 5

Children

• Azithromycin: 20 mg/kg/day (maximum 1g/day) for 7 days 1, 2
• Ceftriaxone: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1, 2
• Cefixime: 8 mg/kg/day as single daily dose for 7-14 days 2

Critical Diagnostic Considerations

• Obtain blood cultures before starting antibiotics whenever possible, as they have the highest yield within the first week of symptom onset 1, 3
• For patients with sepsis features, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures 2, 3
• Blood culture sensitivity is limited; bone marrow culture remains the reference standard but is rarely practical 4

Monitoring and Expected Response

• Expect fever clearance within 4-5 days of appropriate therapy 1, 3
• Monitor for clinical improvement; if no response by day 5, consider resistance or alternative diagnosis 1
• Complete the full 7-day course to prevent relapse, which occurs in 10-15% of inadequately treated cases 1

Management of Complications

• Intestinal perforation occurs in 10-15% of patients with illness duration exceeding 2 weeks 1
• Surgical intervention with simple excision and closure is required for perforation, reported successful in up to 88.2% of cases 1
• Do not delay surgical consultation if perforation is suspected 1

Common Pitfalls to Avoid

• Never use ciprofloxacin empirically for cases from South or Southeast Asia due to widespread resistance 6, 3, 4
• Do not discontinue antibiotics prematurely; complete the full course even if fever resolves early 1
• Avoid combination typhoid-paratyphoid vaccines; only monovalent S. typhi preparations should be used 6
• Do not rely on Widal test alone for diagnosis; it has poor specificity and sensitivity 8

Adverse Effects and Drug Interactions

• Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 3
• Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1
• Ceftriaxone shows 100% sensitivity in most regions with minimal adverse effects 9, 8

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas, particularly Latin America, Asia, and Africa 6, 1
• Vaccination provides incomplete protection (does not protect against paratyphoid) and should not replace food and water safety precautions 6, 1, 3
• Hand hygiene and appropriate food safety practices remain essential 1

Emerging Resistance Concerns

• Extensively drug-resistant strains have emerged in Pakistan, resistant to both fluoroquinolones and ceftriaxone 4, 9
• Multidrug resistance (to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole) remains common, affecting 58% of isolates in some regions 7
• Always consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 2, 9