What is the first-line management of Salmonella (S.) Typhi infection?

First-Line Management of Salmonella Typhi Infection

Azithromycin is the recommended first-line treatment for typhoid fever (S. typhi infection) due to its lower risk of clinical failure, shorter hospital stay, and lower risk of relapse compared to other antibiotics. 1

Antibiotic Selection Algorithm

The choice of antibiotic should be guided by the following considerations:

1. For fully sensitive S. typhi:

   • First choice: Azithromycin
   • Alternatives: Fluoroquinolones, chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole

2. For quinolone-resistant strains:

   • First choice: Azithromycin
   • Alternatives: Ceftriaxone or cefixime 1

3. For multidrug-resistant strains:

   • First choice: Azithromycin or ceftriaxone
   • Alternative: Cefixime 1

Rationale for Azithromycin as First-Line Therapy

Azithromycin is preferred because:

• Lower risk of clinical failure (OR 0.48; 95% CI, 0.26-0.89)
• Shorter hospital stay (-1.04 days; 95% CI, -1.73 to -0.34 days)
• Lower risk of relapse (OR 0.09; 95% CI, 0.01-0.70) 1
• High effectiveness against ciprofloxacin-resistant strains 2

Geographic Considerations

The choice of empiric therapy should consider regional resistance patterns:

• Fluoroquinolone resistance is common in South and Southeast Asia 1
• Recent data shows high resistance rates to conventional first-line antibiotics (ampicillin, amoxicillin), fluoroquinolones (ciprofloxacin), and third-generation cephalosporins (ceftriaxone, cefotaxime) 2

Treatment Duration and Monitoring

• Treatment should continue for 7-14 days depending on the antibiotic used 1
• Monitor fever clearance time (typically 3-5 days with effective therapy) 1
• Ensure clinical improvement within 48-72 hours of initiating appropriate therapy 1

Important Caveats and Considerations

• Antimotility agents should be avoided in suspected typhoid fever as they may worsen outcomes 3, 1
• Inadequate treatment duration increases the risk of relapse 1
• Breastfeeding should be continued throughout treatment in infants 1
• Resistance patterns vary geographically and are changing over time, with fluoroquinolone resistance becoming increasingly common 3, 2
• Clinical non-response occurs in approximately 10% of patients despite in vitro susceptibility and may require combination antibiotic therapy 1

Special Populations

• Pregnant women: Azithromycin is preferred due to its safety profile 1
• Children: Azithromycin is preferred over fluoroquinolones 1

Prevention

• Asymptomatic carriers in high-risk settings (healthcare workers, food handlers) should be treated according to public health guidance 3, 1
• Typhoid vaccination is recommended for travelers to endemic areas 1
• Food safety practices and proper hand hygiene are essential preventive measures 1

By following these evidence-based recommendations, clinicians can effectively manage S. typhi infections while minimizing the risk of complications and antimicrobial resistance.