What is the treatment for enteric fever?

Treatment of Enteric Fever

For suspected enteric fever with sepsis, initiate broad-spectrum antimicrobial therapy immediately after obtaining blood, stool, and urine cultures, then narrow therapy based on susceptibility results. 1

Initial Empiric Treatment Selection

The choice of empiric antibiotic depends critically on local resistance patterns and travel history:

First-Line Options by Clinical Scenario

For mild-to-moderate cases in areas with high fluoroquinolone resistance (most of South and Southeast Asia):

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line therapy 2, 3
• Azithromycin demonstrates 94% cure rates, lower clinical failure rates (OR 0.48) compared to fluoroquinolones, shorter hospital stays, and significantly lower relapse rates (OR 0.09) compared to ceftriaxone 3, 4

For severe cases requiring hospitalization:

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days 2, 3, 5
• For adults: ceftriaxone 1-2g every 12-24 hours based on severity 5
• Switch to oral therapy once clinically improved and afebrile for 24 hours 3, 5

For fully susceptible strains (rare, requires confirmed susceptibility):

• Fluoroquinolones (ciprofloxacin or ofloxacin) may be used, but over 70% of S. typhi isolates globally are now resistant 3, 5, 6
• Ciprofloxacin is FDA-approved for typhoid fever 7

Critical Resistance Considerations

Avoid fluoroquinolones empirically for cases from South Asia due to resistance rates exceeding 90% in many regions 3, 5, 6. Studies show 97.8% resistance to ciprofloxacin and 89-91% resistance to ofloxacin in endemic areas 6. The gyrA ser83 mutation is present in 95.65% of S. typhi isolates, conferring fluoroquinolone resistance 6.

Treatment Duration and Monitoring

• Most uncomplicated cases require 5-7 days of appropriate antibiotics 5
• Azithromycin courses are typically 7 days 2, 3
• Ceftriaxone courses are 5-7 days 2, 3, 5
• Expect fever clearance within 4-5 days of appropriate therapy 3

Diagnostic Approach Before Treatment

• Always obtain blood cultures before initiating antibiotics when possible 3, 5
• Also collect stool and urine cultures in suspected sepsis cases 1, 2
• Modify therapy when susceptibility results become available 1, 5

Special Populations

Children (ages 1-17 years):

• Azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days for mild-moderate cases 3
• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for severe cases 3
• Cefixime 8 mg/kg/day as single daily dose is an alternative oral option 3

Infants <3 months:

• Third-generation cephalosporin is recommended 1

Alternative Agents (When First-Line Options Unavailable)

• Cefixime 400mg orally once daily for adults, or 8 mg/kg/day for children, for 7-14 days 3
• Chloramphenicol may be considered as last-resort when no other options available, though recent data shows re-emerging susceptibility (98.8% susceptible in some regions) 3, 8
• Conventional first-line drugs (ampicillin, chloramphenicol, cotrimoxazole) show renewed susceptibility (97.8% in recent studies) but require large-scale clinical validation before routine use 6, 8

Common Pitfalls to Avoid

• Do not use ciprofloxacin empirically without confirmed susceptibility, especially for travel-related cases from endemic regions 3, 5
• Do not rely on clinical presentation alone—obtain cultures to confirm diagnosis and guide therapy 3, 5
• Do not discontinue antibiotics prematurely before symptom resolution 5
• Do not assume fluoroquinolone susceptibility based on older data—resistance is now the norm in most endemic areas 3, 6

Monitoring for Complications

• For persistent fever, leukocytosis, or signs of peritoneal irritation despite treatment, consider CT imaging to identify intra-abdominal complications 5
• Reassess fluid and electrolyte balance in patients with persistent symptoms 1
• Rehydration with isotonic IV fluids is crucial for severe dehydration 5