What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin 500 mg once daily for 7-14 days is the preferred first-line treatment for typhoid fever in adults, given widespread fluoroquinolone resistance exceeding 70% in endemic regions. 1, 2, 3

First-Line Antibiotic Therapy

Adults

• Azithromycin 500 mg orally once daily for 7-14 days 1, 2, 3
• This regimen demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter with azithromycin (mean difference -1.04 days) 1, 2
• Relapse risk is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 2, 3

Children

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally once daily for 7 days 1, 2, 3

Why Azithromycin Over Fluoroquinolones

Do not use ciprofloxacin empirically for cases originating from South or Southeast Asia - resistance rates exceed 70% in South Asia and approach 96% in some regions 1, 2, 3. Despite FDA approval for typhoid fever 4, ciprofloxacin is empirically inappropriate for travel-associated cases from endemic areas due to widespread resistance 1, 2.

• Fluoroquinolone resistance has rendered ciprofloxacin unreliable in most endemic regions 1, 2, 3
• Ciprofloxacin disc testing is unreliable; only isolates also sensitive to nalidixic acid should be considered fluoroquinolone-sensitive 3
• Over 70% of S. typhi and S. paratyphi isolates imported into the UK are fluoroquinolone-resistant 3

Alternative Therapy for Severe Cases

Ceftriaxone (for severe illness or when oral therapy not tolerated)

• Adults: 1-2g IV/IM once daily for 5-7 days 2, 3
• Children: 50-80 mg/kg/day (maximum 2g/day) IV/IM once daily for 5-7 days 2, 3
• Ceftriaxone may result in decreased clinical failure compared to azithromycin 5
• Time to defervescence may be shorter with ceftriaxone compared to azithromycin (mean difference -0.52 days) 5
• A flexible-duration approach (continuing until defervescence plus 5 additional days) is effective 6
• Mean defervescence time is approximately 4-5 days 6, 7

Critical Diagnostic Steps

Obtain blood cultures before initiating antibiotics whenever possible - they have the highest yield (40-80% sensitivity) within the first week of symptom onset 1, 2, 3. For patients with sepsis features, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures 2.

Expected Clinical Response and Monitoring

• Fever should clear within 4-5 days of appropriate antibiotic therapy 1, 2, 3
• If no clinical response by day 5, consider antibiotic resistance or alternative diagnosis 2
• Monitor for common azithromycin adverse effects: nausea, vomiting, abdominal pain, and diarrhea 1, 2, 3
• Watch for potential drug interactions with azithromycin, particularly QT-prolonging medications 1, 2

Critical Pitfalls to Avoid

Complete the full 7-14 day antibiotic course even if fever resolves early - relapse occurs in 10-15% of inadequately treated cases 1, 2. Premature discontinuation is a common error that leads to treatment failure.

• Never use cefixime as first-line therapy - it has documented treatment failure rates of 4-37.6% and requires mandatory test-of-cure at 1 week if used 2, 5
• Cefixime may result in increased clinical failure (RR 13.39), microbiological failure (RR 4.07), and relapse (RR 4.45) compared to fluoroquinolones 5
• Time to defervescence with cefixime may be 1.74 days longer compared to fluoroquinolones 5

Management of Complications

Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 2. This requires immediate surgical intervention with simple excision and closure, which is successful in up to 88.2% of cases 1, 2.

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa), particularly those with moderate to high risk of exposure 1, 2, 3
• Two vaccines are available in the United States: Ty21a oral vaccine and Vi-polysaccharide parenteral vaccine 1
• Vaccination provides only 50-80% protection and does not protect against Salmonella Paratyphi 1, 3
• Hand hygiene and food/water safety precautions remain essential and should not be replaced by vaccination alone 1, 2

Ty21a Oral Vaccine Dosing

• Adults and children ≥10 years: one enteric-coated capsule taken on alternate days for a total of four capsules 8
• Each capsule should be taken with cool liquid no warmer than 37°C, approximately 1 hour before a meal 8
• Capsules must be kept refrigerated, and all four doses must be taken to achieve maximum efficacy 8
• Booster: repeat the entire four-dose series every 5 years 8

Parenteral Inactivated Vaccine Dosing

• Adults and children ≥10 years: 0.5 ml subcutaneously, given on two occasions separated by ≥4 weeks 8
• Children <10 years: 0.25 ml subcutaneously, given on two occasions separated by ≥4 weeks 8
• Booster: single dose every 3 years under conditions of continued exposure 8

Resistance Pattern Considerations

Always consider local resistance patterns when selecting empiric therapy - these vary geographically and change over time 1, 2. Extensively drug-resistant strains have emerged in Pakistan 5, making surveillance of local resistance patterns essential for optimal treatment selection.