What is the recommended treatment for enteric fever?

Treatment of Enteric Fever

For patients with enteric fever, empiric treatment with a fluoroquinolone (such as ciprofloxacin) or azithromycin is recommended, with the choice depending on local antimicrobial susceptibility patterns and travel history. 1

First-Line Treatment Options

Adults:

• Fluoroquinolone (if susceptible):
  • Ciprofloxacin 500mg twice daily for 10-14 days 2, 3, 4
  • Ofloxacin 400mg twice daily for 7-14 days 1

Children:

• Age <3 months: Third-generation cephalosporin (e.g., ceftriaxone) 1
• Age ≥3 months: Azithromycin, depending on local susceptibility patterns 1

Treatment Algorithm Based on Resistance Patterns

1. Fully susceptible S. typhi:

   • Fluoroquinolone (ciprofloxacin or ofloxacin) 1

2. Multidrug-resistant strains:

   • Fluoroquinolone or cefixime 1
   • Alternative: Azithromycin 1

3. Quinolone-resistant strains:

   • Azithromycin or ceftriaxone 1
   • Alternative: Cefixime 1

Clinical Considerations

• Timing: Early treatment is critical as patients treated early in their clinical course have better outcomes than those treated later 1
• Blood cultures: Obtain blood, stool, and urine cultures before initiating antimicrobial therapy 1
• Sepsis: Patients with clinical features of sepsis should receive empiric broad-spectrum antimicrobial therapy immediately after culture collection 1

Comparative Effectiveness

• Fluoroquinolones vs. Azithromycin:

  • Ciprofloxacin is associated with faster fever clearance (median 20.1 hours vs. 90.8 hours) and blood culture clearance compared to azithromycin 5
  • Azithromycin at 500mg daily is effective but associated with delayed treatment response and prolonged bacteremia 5

• Cephalosporins vs. Other Agents:

  • Ceftriaxone may be as effective as azithromycin but with shorter time to defervescence 6
  • Cefixime may be less effective than fluoroquinolones with longer time to defervescence 6

Treatment Duration

• A 10-day course of ciprofloxacin (500mg twice daily) appears to be as effective as a 14-day course for both sensitive and multidrug-resistant Salmonella, with similar defervescence times and cure rates 4
• Shorter courses (7 days) of ciprofloxacin have shown promising results with rapid defervescence (median: 4 days) and high cure rates (96%) 3

Monitoring and Follow-up

• Monitor for defervescence of fever (typically occurs within 4-5 days of appropriate treatment) 4
• Reassess fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy in patients with persistent symptoms 1

Important Caveats and Pitfalls

• Resistance concerns: Local resistance patterns should guide empiric therapy choice, as resistance to fluoroquinolones is increasing, particularly in South Asia 6
• Delayed treatment: Avoid delaying antimicrobial therapy when infection is strongly suspected in critically ill patients 7
• Relapse risk: Even with appropriate treatment, relapse can occur (reported in some studies with both ciprofloxacin and azithromycin) 5, 4
• Carrier state: The efficacy of ciprofloxacin in eradicating the chronic typhoid carrier state has not been demonstrated 2

Remember that early and appropriate antimicrobial therapy significantly reduces morbidity and mortality in enteric fever compared to supportive treatment alone or inadequate dosing 1.