What is the recommended treatment for enteric fever?

Treatment of Enteric Fever

First-Line Treatment Recommendations

For uncomplicated enteric fever, 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 such as South Asia. 1

Outpatient/Mild-Moderate Cases

• Azithromycin is the optimal choice with a 94% cure rate and significantly lower relapse risk (OR 0.09) compared to ceftriaxone 1
• Dosing: 20 mg/kg/day (maximum 1g/day) orally for 7 days 1
• This agent demonstrates lower clinical failure rates (OR 0.48) and shorter hospital stays compared to fluoroquinolones 1

Inpatient/Severe Cases

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is the first-line therapy for hospitalized patients 2
• For adults: 1-2g every 12-24 hours based on severity 2
• Switch to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours 1

Critical Diagnostic Steps

• Always obtain blood cultures before initiating antibiotics 1, 2
• For suspected sepsis, also collect stool and urine cultures 1
• Start broad-spectrum antimicrobial therapy immediately after culture collection in septic patients, then narrow based on susceptibility results 1, 2

Alternative Treatment Options Based on Resistance Patterns

When Fluoroquinolones Can Be Used (Fully Susceptible Strains Only)

• Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi 3
• A 7-day course of ciprofloxacin 500mg twice daily shows 96% cure rate with rapid defervescence (median 4 days) 4
• However, over 70% of S. typhi isolates in many regions are now fluoroquinolone-resistant, making empiric use inappropriate 1, 2
• Avoid ciprofloxacin empirically for cases from South Asia due to high resistance rates 1, 2

Oral Cephalosporin Option

• Cefixime 8 mg/kg/day as a single daily dose for 7-14 days can be used as an oral alternative 1
• Adult dosing: 400mg orally once daily 1
• However, cefixime may have increased clinical failure (RR 13.39), microbiological failure (RR 4.07), and relapse (RR 4.45) compared to fluoroquinolones in susceptible strains 5
• Time to defervescence is 1.74 days longer with cefixime versus fluoroquinolones 5

Treatment Duration and Monitoring

• Most patients with uncomplicated enteric fever require 7 days of appropriate antibiotics 1
• For parenteral therapy: 5-7 days, then switch to oral as described above 1, 2
• Expected fever clearance within 4-5 days of appropriate therapy 1

Special Populations

Infants Under 3 Months

• Must use a third-generation cephalosporin (ceftriaxone) 1

Children (1-17 Years)

• Azithromycin 20 mg/kg/day for 7 days or ceftriaxone 50-80 mg/kg/day for 5-7 days 1
• Fluoroquinolones are not first-choice in pediatrics due to increased adverse events including joint-related complications 3

Comparative Effectiveness: Ceftriaxone vs. Azithromycin

• Ceftriaxone may result in decreased clinical failure compared to azithromycin (RR 0.42) 5
• Time to defervescence is 0.52 days shorter with ceftriaxone versus azithromycin 5
• However, relapse rates may be higher with ceftriaxone (RR 10.05) 5
• Both are acceptable options; choice depends on severity and route preference 1, 2

Emerging Resistance and Extensively Drug-Resistant (XDR) Strains

• XDR enteric fever has emerged in Pakistan since 2016, responding only to limited antibiotics 6
• Fluoroquinolone resistance is essentially a class effect and increasing globally 1
• Always modify therapy when susceptibility results become available 1, 2
• Local resistance patterns must guide empiric therapy selection as these vary geographically and change over time 1, 2

Common Pitfalls to Avoid

• Do not use fluoroquinolones empirically without confirmed susceptibility, especially for infections acquired in South Asia 1, 2
• Do not rely solely on clinical presentation; cultures are essential 1, 2
• Avoid premature discontinuation before complete symptom resolution 2
• Do not forget to reassess fluid and electrolyte balance in patients with persistent symptoms 1
• For persistent fever, leukocytosis, or peritoneal signs, consider CT imaging for intra-abdominal complications 2

Supportive Care

• Rehydration with isotonic intravenous fluids for severe dehydration 2
• Monitor for complications including intestinal perforation, bleeding, confusion, or bone infection 6