What is the recommended treatment for enteric fever?

Treatment of Enteric Fever

For patients with enteric fever, empiric treatment with a fluoroquinolone (ciprofloxacin or ofloxacin) or azithromycin should be initiated after blood, stool, and urine culture collection, with therapy adjusted based on antimicrobial susceptibility testing results. 1

Initial Management

• Patients with clinical features of sepsis who are suspected of having enteric fever should receive empiric broad-spectrum antimicrobial therapy after appropriate cultures are collected 1
• Antimicrobial therapy should be narrowed when susceptibility testing results become available 1
• If culture results are unavailable, antimicrobial choice should be tailored to susceptibility patterns from the setting where acquisition occurred 1

Empiric Antibiotic Selection

First-line options:

• Fluoroquinolones: Ciprofloxacin 500 mg twice daily for 7-10 days or ofloxacin 400 mg twice daily for 7-10 days 1, 2, 3, 4
  • Particularly effective in areas without significant quinolone resistance
  • FDA-approved indication for typhoid fever (enteric fever) caused by Salmonella typhi 2
• Azithromycin: Consider as first-line therapy in areas with known fluoroquinolone resistance 1
  • Particularly important in regions with high rates of fluoroquinolone-resistant Campylobacter and other enteric pathogens 1
  • Lower risk of clinical failure (OR 0.48) and shorter hospital stay compared to fluoroquinolones in some studies 1

Second-line options:

• Third-generation cephalosporins: Ceftriaxone or cefixime when resistance to first-line agents is suspected 1
• In children <3 months of age, a third-generation cephalosporin is preferred 1

Considerations for Treatment Selection

• Local susceptibility patterns should guide therapy choice 1
• Travel history should be considered when selecting empiric therapy 1
• Recent emergence of extensively drug-resistant (XDR) strains, particularly from Pakistan since 2016, may require alternative treatment approaches 5
• Duration of treatment typically ranges from 7-14 days depending on clinical response and antimicrobial agent used 3, 4

Monitoring and Response

• Most patients show clinical improvement with defervescence within 4-5 days of appropriate therapy 3, 4
• Reassessment of fluid and electrolyte balance, nutritional status, and optimal dose and duration of antimicrobial therapy is recommended in people with persistent symptoms 1
• Reduced osmolarity oral rehydration solution (ORS) is recommended as first-line therapy for mild to moderate dehydration 1
• For severe dehydration, shock, or altered mental status, isotonic intravenous fluids should be administered 1

Special Considerations

• Relapse can occur in approximately 5-10% of treated patients, even with appropriate therapy 3, 4
• Some patients may become chronic carriers and require extended treatment courses 5
• Antimicrobial resistance patterns have changed significantly over time, with increasing resistance to traditional first-line agents 6, 5
• Fluoroquinolones remain effective in many regions but resistance is increasing globally 6

Prevention

• Travelers to endemic regions should follow safe food and water practices and consider typhoid vaccination at least several weeks before travel 5
• Asymptomatic contacts of people with enteric fever should not be offered empiric treatment but should follow appropriate infection prevention and control measures 1