What is the recommended treatment regimen with doses for enteric fever?

Treatment for Enteric Fever with Dosing

For enteric fever, azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line treatment for mild-to-moderate cases, while ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days should be used for severe cases requiring hospitalization. 1, 2, 3

Initial Diagnostic Approach

• Always obtain blood cultures before initiating antibiotics to confirm diagnosis and guide antimicrobial therapy 1, 3
• For patients with clinical features of sepsis, initiate broad-spectrum antimicrobial therapy immediately after blood culture collection, then narrow therapy based on susceptibility results 4, 1, 3
• Consider enteric fever in any febrile patient with travel history to endemic areas, particularly South Asia 3

First-Line Treatment Selection

For Mild-to-Moderate Cases (Outpatient or Stable Inpatient)

Azithromycin is the preferred first-line agent:

• Dosing: 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2, 3
• Demonstrates 94% cure rate in children with typhoid fever 2, 3
• Shows significantly lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones 4
• Lower risk of relapse (OR 0.09) compared to ceftriaxone 4

For Severe Cases (Hospitalized Patients)

Ceftriaxone is the first-line therapy:

• Dosing: 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days 1, 2, 3
• For adults: 1-2g IV every 12-24 hours based on severity 1
• Expected fever clearance within 4-5 days of appropriate therapy 2, 3

Alternative Treatment Options Based on Resistance Patterns

Fluoroquinolones (Use Only in Fully Susceptible Strains)

Critical caveat: Over 70% of S. typhi isolates in many regions are now resistant to fluoroquinolones, making them inappropriate for empiric therapy in most settings 1, 2, 3

When susceptibility is confirmed:

• Ciprofloxacin: 500 mg orally twice daily for 10-14 days (adults) 5
• Ofloxacin or gatifloxacin may be used in areas with documented susceptibility 4
• Avoid fluoroquinolones empirically for cases originating from South Asia due to high resistance rates 1, 2, 3

Oral Cephalosporin Alternative

Cefixime:

• Dosing: 8 mg/kg/day as a single daily dose for 7-14 days (children) 2
• Adults: 400 mg orally once daily 2
• May have higher clinical failure rates compared to fluoroquinolones in resistant areas 6

Special Population Considerations

Infants Under 3 Months

• Use third-generation cephalosporin (ceftriaxone) as first-line 4, 2, 3
• Dosing: 50-80 mg/kg/day IV 2, 3

Children

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is preferred 2, 3
• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days for severe cases 2, 3

Treatment Duration and Monitoring

• Most patients with uncomplicated enteric fever should receive 7 days of appropriate antibiotics 1, 3
• For ceftriaxone, 5-7 days is the recommended duration 1, 3
• Transfer from IV to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours 1, 2
• Expected fever clearance within 4-5 days of appropriate therapy 2, 3

Comparative Effectiveness Evidence

Azithromycin vs. Fluoroquinolones

• Azithromycin shows lower risk of clinical failure (OR 0.48,95% CI 0.26-0.89) and shorter hospital stay (-1.04 days) compared to fluoroquinolones 4

Ceftriaxone vs. Azithromycin

• Ceftriaxone may result in decreased clinical failure compared to azithromycin 6
• Time to defervescence may be 0.52 days shorter with ceftriaxone 6
• However, azithromycin shows lower relapse rates (OR 0.09) 4

Ceftriaxone vs. Fluoroquinolones

• In culture-confirmed cases from Nepal, ceftriaxone was associated with lower risk of failure (HR 0.24,95% CI 0.08-0.73) compared to gatifloxacin 4, 7
• This trial was stopped early due to emergence of high-level fluoroquinolone resistance 4, 7

Supportive Care

• Evaluate all patients for dehydration, which increases risk of life-threatening illness 3
• Use isotonic intravenous fluids for severe dehydration 3
• Reassess fluid and electrolyte balance in patients with persistent symptoms 2

Common Pitfalls to Avoid

• Do not use fluoroquinolones empirically for cases originating from South Asia due to resistance rates exceeding 70% 1, 2, 3
• Do not rely solely on clinical presentation for diagnosis—obtain cultures whenever possible 1, 2, 3
• Avoid premature discontinuation of antibiotics before complete resolution of symptoms 1
• Always modify therapy when susceptibility results become available 4, 1, 3
• Consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1, 2, 3