What is the recommended treatment for enteric fever?

Treatment of Enteric Fever

Immediate Management for Suspected Enteric Fever

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

Initial Diagnostic Steps

• Obtain blood cultures before starting antibiotics whenever possible to confirm diagnosis and guide therapy 2, 3
• Consider enteric fever in any febrile patient with travel history to endemic areas (particularly South Asia), consumption of foods prepared by people with recent endemic exposure, or laboratory exposure to Salmonella typhi or Paratyphi 3
• Assess for dehydration, which increases risk of life-threatening complications, especially in young children and older adults 3

First-Line Treatment Selection

For Hospitalized/Severe Cases

Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is the preferred first-line therapy for patients requiring inpatient treatment. 2, 3

• For adults, ceftriaxone 1-2g every 12-24 hours is appropriate based on severity 2
• Expected fever clearance occurs within 4-5 days of appropriate therapy 3, 4
• Switch to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours 2

For Mild to Moderate Outpatient Cases

Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line therapy, particularly in regions with high fluoroquinolone resistance. 3

• Azithromycin demonstrates a 94% cure rate and significantly lower relapse risk compared to ceftriaxone 3
• Can also be used as step-down therapy after initial IV treatment 2
• Recent data shows 98.1% effectiveness in treating extensively drug-resistant (XDR) enteric fever 5

Treatment Based on Resistance Patterns

Critical Resistance Considerations

• Over 70% of S. typhi isolates in many regions are now resistant to fluoroquinolones, making ceftriaxone or azithromycin better empiric choices 2
• Avoid using fluoroquinolones empirically for cases originating from South Asia due to high resistance rates 2
• Since 2016, there has been an ongoing outbreak of XDR enteric fever in Pakistan that only responds to limited antibiotics 6
• Modify antimicrobial therapy when susceptibility testing results become available 1, 2

Alternative Options (When Susceptibility Known)

• Fluoroquinolones (ciprofloxacin or ofloxacin) may be considered only in areas with documented susceptibility 2, 7
• Local susceptibility patterns should guide therapy choice, as resistance varies geographically and changes over time 2, 7

Special Populations

Infants and Children

• Infants <3 months of age should receive a third-generation cephalosporin (ceftriaxone) 1, 3
• Azithromycin or ceftriaxone are preferred options in children 3
• Cefixime is commonly used in outpatient settings, though approximately 10% may require additional antibiotics due to clinical non-response 8

Immunocompromised Patients

• Consider empiric antibacterial treatment in immunocompromised people with severe illness 1

Supportive Care and Monitoring

Rehydration

• Evaluate all patients for dehydration status 3
• Isotonic intravenous fluids (lactated Ringer's or normal saline) are recommended for severe dehydration, shock, or altered mental status 1, 3
• Reduced osmolarity oral rehydration solution (ORS) is first-line therapy for mild to moderate dehydration 1

Monitoring for Complications

• For patients with persistent or recurrent signs of peritoneal irritation, failure of bowel function to return to normal, continued fever or leukocytosis, consider CT imaging to identify persistent or new intra-abdominal infection 2
• Reassess fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy in patients with persistent symptoms 1
• Clinical non-response occurs in approximately 10% of patients who may need combination antibiotics 8

Treatment Duration

• Most patients with uncomplicated enteric fever should receive 5-7 days of appropriate antibiotics 2, 3
• Ceftriaxone: 5-7 days 2, 3, 4
• Azithromycin: 7 days 3
• Avoid premature discontinuation before complete resolution of symptoms 2

Common Pitfalls to Avoid

• Do not rely solely on clinical presentation for diagnosis; obtain cultures whenever possible 2
• Do not use fluoroquinolones empirically without knowing susceptibility patterns, especially for South Asian travel 2
• Do not delay antimicrobial therapy in septic patients while waiting for culture results 1
• Ensure good compliance and complete dosage to avoid resistance development, particularly with azithromycin 5
• Always send blood cultures when prescribing antibiotics for suspected enteric fever 5