What is the treatment for typhoid fever?

Treatment of Typhoid Fever

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

First-Line Treatment Algorithm

Initial Management

• Collect blood cultures immediately before starting antibiotics, as they have the highest diagnostic yield (40-80% sensitivity) within the first week of symptom onset 2, 3
• Do not delay treatment in severely ill patients—start empiric therapy after obtaining cultures 3
• Begin azithromycin 500 mg once daily for 7 days in adults 1, 2, 3
• For children: azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days 1, 2, 3

Why Azithromycin is Preferred

• Azithromycin demonstrates superior clinical outcomes with significantly lower risk of clinical failure (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter with azithromycin (mean difference -1.04 days) compared to fluoroquinolones 1, 2
• Relapse risk is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 2
• Fever clearance time with azithromycin (5.8 days) is shorter than cefixime (7.1 days) and ciprofloxacin (8.2 days) 4

Geographic Resistance Patterns: Critical for Treatment Selection

South and Southeast Asia

• Never use ciprofloxacin empirically for cases from South or Southeast Asia—fluoroquinolone resistance exceeds 70% in these regions, with some areas approaching 96% 1, 3
• Over 70% of S. typhi and S. paratyphi isolates imported from South Asia are fluoroquinolone-resistant 2, 3
• In Thailand specifically, 93% of isolates were ciprofloxacin-resistant 1

When Fluoroquinolones May Be Considered

• Fluoroquinolones (ciprofloxacin or ofloxacin) remain effective only when susceptibility is confirmed by culture 1
• Ciprofloxacin disc testing is unreliable—only isolates also sensitive to nalidixic acid should be considered fluoroquinolone-sensitive 2
• Levofloxacin may be considered only when culture confirms susceptibility and the case is not from South or Southeast Asia 1

Alternative Treatment Options

Severe Cases Requiring IV Therapy

• Ceftriaxone 1-2g IV/IM daily for 5-7 days in adults 1, 2
• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days in children 1, 2

Ceftriaxone Performance

• Ceftriaxone may result in decreased clinical failure compared to azithromycin (RR 0.42), though evidence is from older trials 5
• Time to defervescence with ceftriaxone may be 0.52 days shorter compared to azithromycin 5
• However, relapse risk may be higher with ceftriaxone compared to azithromycin (OR 0.09 favoring azithromycin) 1

Cefixime: Use with Caution

• Cefixime has documented treatment failure rates of 4-37.6% in clinical practice 1
• Clinical failure is significantly increased with cefixime compared to fluoroquinolones (RR 13.39) 5
• Relapse rates with cefixime are elevated (RR 4.45 compared to fluoroquinolones) 5
• If cefixime must be used, a mandatory test-of-cure at 1 week is required due to high failure rates 1
• The WHO lists cefixime only as an "alternative" option, not first-line 1

Monitoring and Expected Clinical Response

Timeline for Improvement

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2, 3
• If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Complete the full 7-day course even if fever resolves early to prevent relapse, which occurs in 10-15% of inadequately treated cases 1

Common Adverse Effects

• Gastrointestinal symptoms are common with azithromycin: nausea, vomiting, abdominal pain, and diarrhea 1, 2
• Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely—complete the full 7-day course even if fever resolves early 1
• Never use ciprofloxacin empirically for cases from South or Southeast Asia due to widespread resistance 1, 3
• Do not rely on ciprofloxacin disc testing alone for susceptibility determination 2
• Treatment failure with fluoroquinolones in resistant strains results in significantly prolonged illness (76.4 hours vs 41.2 hours for susceptible strains) 1

Complications Requiring Surgical Intervention

• 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, with success rates up to 88.2% 1

Prevention Strategies

Vaccination Recommendations

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) 1, 2, 3
• Two vaccines available: Ty21a oral vaccine (four capsules on alternate days, booster every 5 years) and Vi-polysaccharide parenteral vaccine (0.5 ml subcutaneously, booster every 3 years) 1
• Vaccination provides only 50-80% protection and does not protect against Salmonella Paratyphi—hand hygiene and food/water safety precautions remain essential despite vaccination 1, 2, 3
• Ty21a oral vaccine capsules must be kept refrigerated and taken with cool liquid no warmer than 37°C, approximately 1 hour before meals 1