What is the recommended management for enteric fever?

Management of Enteric Fever

Intravenous ceftriaxone is the preferred first-line treatment for enteric fever, especially for patients with severe illness or those returning from regions with high fluoroquinolone resistance such as Asia. 1

Diagnosis and Initial Assessment

• Blood cultures should be collected before starting antibiotics, as they have the highest yield within the first week of symptoms 1
• Stool and urine cultures become positive after the first week of illness, with lower sensitivity than blood cultures 1
• The Widal serological test lacks sensitivity and specificity and is not recommended 1
• Bone marrow cultures have higher sensitivity than blood cultures but are more invasive 1

Empiric Antibiotic Therapy

First-line Treatment Options:

• For hospitalized patients or severe illness:

  • Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days 2, 3
  • Continue treatment for 14 days to reduce risk of relapse 1

• For uncomplicated cases (oral therapy):

  • Azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days 2, 3
  • Azithromycin has shown lower risk of clinical failure compared to fluoroquinolones 2, 3

Alternative Options Based on Susceptibility:

• If fluoroquinolone-sensitive (confirmed by nalidixic acid sensitivity testing):

  • Ciprofloxacin 500 mg twice daily for 7-10 days 3, 4, 5
  • Offers average fever clearance time of <4 days and cure rates >96% 1

• If fluoroquinolone resistance is confirmed:

  • Azithromycin is a suitable oral alternative 1
  • Cefixime can be used but has reported treatment failure rates of 4-37.6% 1, 6

Important Considerations

• Over 70% of S. typhi and S. paratyphi isolates imported to the UK are resistant to fluoroquinolones 1
• Patients with clinical features of sepsis should receive broad-spectrum antimicrobial therapy immediately after blood culture collection 1, 3
• Antimicrobial therapy should be narrowed when susceptibility testing results become available 1
• Resistance patterns vary geographically and are changing over time - local resistance patterns should guide therapy choice 7, 6

Monitoring and Complications

• Monitor for complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy, which occur in 10-15% of patients 1, 8
• Complications are more likely if duration of illness exceeds 2 weeks 1
• Reassess fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy in patients with persistent symptoms 1
• The addition of steroids may be helpful in severe cases 1

Relapse Prevention and Follow-up

• Relapse rates: ceftriaxone <8%, azithromycin <3%, fluoroquinolones variable 1
• Treatment should be continued for 14 days to reduce risk of relapse 1
• Follow-up testing is not recommended in most people following resolution of symptoms 1
• Collection of serial stool specimens may be required by local health authorities to enable return to child care, employment, or group activities 1

Common Pitfalls to Avoid

• Avoid empiric fluoroquinolone use for cases originating from South Asia due to high resistance rates 1, 2, 6
• Do not rely on ciprofloxacin disc testing alone to determine Salmonella sensitivity; nalidixic acid sensitivity must also be confirmed 1
• Do not use the Widal serological test due to poor sensitivity and specificity 1
• Asymptomatic contacts should not be offered empiric treatment but should follow appropriate infection prevention measures 1