What is the recommended treatment for enteric fever?

Treatment of Enteric Fever

First-Line Empiric Treatment

For uncomplicated enteric fever, azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the recommended first-line therapy, particularly in regions with high fluoroquinolone resistance. 1

• Azithromycin demonstrates a 94% cure rate in children with typhoid fever and significantly lower relapse risk (OR 0.09) compared to ceftriaxone 1
• This agent shows lower clinical failure rates (OR 0.48) and shorter hospital stays compared to fluoroquinolones in systematic reviews 1
• Azithromycin is highly effective against extensively drug-resistant (XDR) Salmonella, with 98.1% effectiveness demonstrated in recent studies 2

Severe Cases Requiring Hospitalization

For patients requiring inpatient treatment or presenting with sepsis, ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is the preferred initial therapy. 1, 3

• For adults, ceftriaxone 1-2g every 12-24 hours is appropriate based on severity 3
• Blood cultures should be obtained before initiating antibiotics whenever possible 1, 3
• Broad-spectrum antimicrobial therapy should be started immediately after blood culture collection in patients with clinical features of sepsis 1, 3

Alternative Oral Options

Cefixime 8 mg/kg/day as a single daily dose for 7-14 days can be used as an alternative oral option, though it may not perform as well as fluoroquinolones or azithromycin. 1, 4

• For adults, cefixime 400 mg orally in a single dose is typically recommended 1
• Clinical failure, microbiological failure, and relapse may be increased with cefixime compared to fluoroquinolones (RR 13.39,95% CI 3.24 to 55.39 for clinical failure) 4
• Time to defervescence may be longer with cefixime compared to fluoroquinolones (mean difference 1.74 days) 4

Fluoroquinolone Use: Geographic Considerations

Fluoroquinolones (ciprofloxacin 500 mg twice daily for 7 days or ofloxacin) should only be used for fully susceptible S. typhi strains, and are NOT recommended for empiric therapy in South Asia due to widespread resistance. 1, 5, 6

• Over 70% of S. typhi isolates in many regions are now resistant to fluoroquinolones 1, 3
• Ciprofloxacin is FDA-approved for typhoid fever caused by Salmonella typhi 5
• In populations with nalidixic acid resistance (NaR), fluoroquinolones show higher clinical failure rates compared to azithromycin (RR 2.20,95% CI 1.23 to 3.94) 6
• Gatifloxacin may remain effective in some regions where resistance to older fluoroquinolones has developed 6

Treatment Duration and Transition to Oral Therapy

Most patients with uncomplicated enteric fever require 7 days of appropriate antibiotics, with transition to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours. 1, 3

• Expected fever clearance occurs within 4-5 days of appropriate therapy 1
• Patients initially treated with parenteral antibiotics should be transferred to oral regimen as soon as clinically appropriate 1, 3

Special Populations

Infants under 3 months should be treated with a third-generation cephalosporin. 1

Critical Pitfalls to Avoid

• Never use ciprofloxacin empirically for cases originating from South Asia due to resistance rates exceeding 70% 1, 3
• Always obtain blood cultures before starting antibiotics when possible; also collect stool and urine cultures in suspected sepsis cases 1, 3
• Do not rely solely on clinical presentation for diagnosis—microbiological confirmation is essential 1, 3
• Modify therapy when susceptibility results become available rather than continuing empiric treatment 1, 3
• Consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1, 3
• Avoid premature discontinuation of antibiotics before complete resolution of symptoms 3

Monitoring and Complications

• Reassess fluid and electrolyte balance in patients with persistent symptoms 1
• For patients with persistent peritoneal irritation, failure of bowel function to normalize, or continued fever/leukocytosis, consider CT imaging to identify persistent or new intra-abdominal infection 3
• Isotonic intravenous fluids are recommended for severe dehydration 3