Treatment of Enteric Fever
Immediate Management
For patients with suspected enteric fever and clinical features of sepsis, initiate broad-spectrum antimicrobial therapy immediately after obtaining blood, stool, and urine cultures. 1
First-Line Empiric Treatment
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 severe enteric fever requiring hospitalization. 2, 3
- For adults, administer ceftriaxone 1-2g every 12-24 hours based on severity. 3
- This recommendation is particularly important given that over 70% of S. typhi isolates globally now show fluoroquinolone resistance. 2, 3
For Mild-to-Moderate Cases (Outpatient)
- Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the first-line therapy for uncomplicated enteric fever, especially in areas with high fluoroquinolone resistance. 2
- Azithromycin demonstrates a 94% cure rate and significantly lower relapse risk (OR 0.09) compared to ceftriaxone. 2
- Azithromycin also shows lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones. 2
Alternative Oral Option
- Cefixime 8 mg/kg/day as a single daily dose (400mg for adults) for 7-14 days is an appropriate oral alternative. 2
Treatment Based on Susceptibility Results
- Narrow antimicrobial therapy once susceptibility testing results become available. 1
- For fully susceptible S. typhi strains, fluoroquinolones (ciprofloxacin or ofloxacin) may be used, but this is increasingly rare. 2
- Fluoroquinolone resistance is essentially a class effect and exceeds 70% in most endemic regions. 2, 3
Treatment Duration and Transition
- Most patients with uncomplicated enteric fever require 5-7 days of appropriate antibiotics. 3
- Transfer patients from parenteral to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours. 2, 3
- Expected fever clearance occurs within 4-5 days of appropriate therapy. 2
Geographic and Resistance Considerations
High-Risk Resistance Patterns
- Avoid empiric fluoroquinolones for cases originating from South Asia due to extremely high resistance rates. 2, 3
- Since 2016, extensively drug-resistant (XDR) enteric fever from Pakistan responds only to limited antibiotics. 4
- Always tailor antimicrobial choice to susceptibility patterns from the setting where acquisition occurred. 1
Local Susceptibility Patterns
- Consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time. 2, 5, 3
Critical Pitfalls to Avoid
- Never use antibiotics empirically for STEC O157 or other Shiga toxin 2-producing organisms, as this is contraindicated. 1
- Do not rely solely on clinical presentation; obtain blood cultures before initiating antibiotics whenever possible. 2, 3
- Avoid premature discontinuation of antibiotics before complete symptom resolution. 3
- Do not use chloramphenicol as first-line therapy; reserve it only as a last-resort option when no other antibiotics are available. 2
Monitoring and Follow-Up
- Reassess fluid and electrolyte balance, nutritional status, and optimal antibiotic dose/duration in patients with persistent symptoms. 1
- For patients not responding to initial therapy, reevaluate clinically and consider noninfectious conditions including inflammatory bowel disease. 1
- Administer isotonic intravenous fluids (lactated Ringer's or normal saline) for severe dehydration or shock. 1
Special Populations
Children
- For infants <3 months with suspected bacterial etiology, use third-generation cephalosporin. 1
- For children with neurologic involvement, use third-generation cephalosporin regardless of age. 1
- Azithromycin dosing remains 20 mg/kg/day (maximum 1g/day) for 7 days. 2
Immunocompromised Patients
- Consider empiric antibacterial treatment in immunocompromised individuals with severe illness and bloody diarrhea. 1