What is the treatment for enteric fever encephalitis?

Treatment of Enteric Fever Encephalitis

Patients with enteric fever and neurologic involvement (encephalitis) should be treated with a third-generation cephalosporin, specifically ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for at least 14 days, with empiric broad-spectrum antimicrobial therapy initiated immediately after blood culture collection. 1, 2

Immediate Management Approach

Initial Empiric Therapy

• Start broad-spectrum antimicrobial therapy immediately after collecting blood, stool, and urine cultures in patients with clinical features of sepsis and suspected enteric fever 1
• Ceftriaxone is the preferred agent for neurologic involvement, given as 50-80 mg/kg/day (maximum 2g/day) intravenously 2, 3
• In children specifically, third-generation cephalosporins are explicitly recommended for those with neurologic involvement 1

Why Ceftriaxone Over Other Options

Fluoroquinolones should be avoided as empiric therapy, particularly for cases originating from South Asia, where over 70% of S. typhi and S. paratyphi isolates are fluoroquinolone-resistant 2, 3, 4

Azithromycin, while effective for uncomplicated enteric fever, is not the optimal choice for neurologic complications. The evidence shows:

• Ceftriaxone may result in decreased clinical failure compared to azithromycin 5
• Time to defervescence is shorter with ceftriaxone (mean difference of -0.52 days) 5
• For severe disease requiring hospitalization or neurologic involvement, parenteral cephalosporins are preferred 2, 3

Treatment Duration and Monitoring

Duration

• Continue treatment for at least 14 days to reduce risk of relapse 2, 3
• Ceftriaxone has relapse rates <8%, significantly lower than fluoroquinolones 2
• Patients treated initially with parenteral antibiotics should be transferred to oral regimen once clinical improvement occurs and temperature has been normal for 24 hours 3

Expected Clinical Response

• Fever should clear within 4-5 days of appropriate therapy 3
• If no improvement occurs, reassess for complications or alternative diagnoses 1

Critical Complications to Monitor

Enteric fever with neurologic involvement requires vigilance for:

• Gastrointestinal bleeding and intestinal perforation (occur in 10-15% of patients) 2
• Typhoid encephalopathy as a specific complication 2
• Complications are more likely if illness duration exceeds 2 weeks before treatment 2

Tailoring Therapy Based on Culture Results

When Susceptibility Results Available

• Narrow antimicrobial therapy when susceptibility testing results become available 1
• If isolate unavailable but clinical suspicion remains, tailor antimicrobial choice to susceptibility patterns from the setting where acquisition occurred 1

Alternative Agents (Based on Susceptibility)

• For fully susceptible strains, fluoroquinolones (ofloxacin or ciprofloxacin) may be used, but resistance is increasingly common 3
• Chloramphenicol may be considered as last-resort when no other antibiotics are available 3

Common Pitfalls to Avoid

• Do not use fluoroquinolones empirically for cases from endemic areas, particularly South Asia, due to widespread resistance 2, 3, 4
• Do not use shorter treatment courses (<14 days) as this increases relapse risk 2, 3
• Do not delay antimicrobial therapy while awaiting culture results in patients with sepsis features 1
• Do not assume clinical improvement means adequate treatment duration—complete the full 14-day course 2, 3

Supportive Care Considerations

While antimicrobial therapy is primary:

• Assess and correct fluid and electrolyte balance aggressively 1
• Monitor neurologic status closely for deterioration requiring intensive care 1
• Consider transfer to neurological unit if diagnosis not rapidly established or patient fails to improve 1