What is the recommended treatment dose for enteric fever in adults?

Treatment Dosing for Enteric Fever in Adults

For adults with suspected enteric fever, initiate azithromycin 1g orally once daily for 7 days as first-line therapy, particularly in regions with high fluoroquinolone resistance, or ceftriaxone 2g IV/IM once daily for 5-7 days for severe cases requiring hospitalization. 1, 2

Initial Management and Diagnostic Approach

• Always obtain blood cultures before starting antibiotics when clinically feasible, along with stool and urine cultures if sepsis is suspected 3, 1
• For patients presenting with sepsis features (fever ≥38.5°C, signs of sepsis), initiate broad-spectrum antimicrobial therapy immediately after culture collection, then narrow based on susceptibility results 3

First-Line Treatment Options Based on Clinical Severity

Mild to Moderate Cases (Outpatient)

• Azithromycin: 1g orally once daily for 7 days (20 mg/kg/day, maximum 1g/day) 1, 2
  • Demonstrates 94% cure rate and significantly lower clinical failure rates (OR 0.48,95% CI 0.26-0.89) compared to fluoroquinolones 3, 4
  • Shows shorter hospital stays (-1.04 days) and lower relapse rates (OR 0.09) compared to ceftriaxone 3, 4
  • Particularly effective against multidrug-resistant and nalidixic acid-resistant strains 5

Severe Cases (Hospitalized/Septic)

• Ceftriaxone: 2g IV/IM once daily for 5-7 days (50-80 mg/kg/day, maximum 2g/day) 1, 2
  • Preferred for patients unable to tolerate oral therapy or with severe illness 1
  • May show shorter time to defervescence (-0.52 days) compared to azithromycin 6

Alternative Treatment Options

When Azithromycin/Ceftriaxone Unavailable or Based on Susceptibility

Fluoroquinolones (if susceptible strains confirmed):

• Ciprofloxacin: 500mg orally twice daily for 7 days 3
• Ofloxacin: 400mg orally twice daily for 7 days 3
• Critical caveat: Over 70% of S. typhi isolates in many regions (particularly South Asia) are now fluoroquinolone-resistant; avoid empiric use in these areas 1

Oral cephalosporin alternative:

• Cefixime: 400mg orally once daily for 7-14 days 1
• Note: May have higher clinical failure rates compared to fluoroquinolones (RR 13.39) and should not be first choice 6

Treatment Duration and Monitoring

• Standard duration: 7 days for uncomplicated cases 1, 2
• Ceftriaxone: 5-7 days is sufficient 1, 2
• Expected fever clearance: 4-5 days after initiating appropriate therapy 1
• Transfer from IV to oral therapy once clinically improved and afebrile for 24 hours 1

Modifying Therapy Based on Results

• Narrow antimicrobial spectrum when susceptibility results become available 3
• If isolate unavailable but clinical suspicion remains, tailor therapy to susceptibility patterns from the acquisition location 3
• Reassess fluid/electrolyte balance and antimicrobial dosing in patients with persistent symptoms 3

Critical Pitfalls to Avoid

• Do not use ciprofloxacin empirically for cases from South Asia due to widespread resistance 1
• Do not rely on older antibiotics (chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole) as empiric therapy—resistance is common and they are no longer recommended by WHO 3
• Do not delay treatment in septic patients waiting for culture results; start broad-spectrum therapy immediately after obtaining cultures 3
• Do not use cefixime as first-line when azithromycin or ceftriaxone are available, as it shows inferior outcomes 6

Comparative Effectiveness Summary

When comparing the main treatment options in recent systematic reviews:

• Azithromycin vs fluoroquinolones: Azithromycin superior with lower clinical failure (OR 0.48) and shorter hospital stays, especially for resistant strains 3, 4
• Azithromycin vs ceftriaxone: Ceftriaxone may have slightly faster fever clearance (-0.52 days), but azithromycin has lower relapse rates (OR 0.09) 3, 4, 6
• Ceftriaxone vs fluoroquinolones: No significant difference in outcomes, but local resistance patterns should guide choice 6