Empiric Treatment of Enteric Fever
The recommended empiric treatment for enteric fever is azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days in areas with high fluoroquinolone resistance, or ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days for severe cases requiring hospitalization. 1
First-Line Treatment Options
- Azithromycin is recommended as first-line therapy in areas with known fluoroquinolone resistance, with lower risk of clinical failure and shorter hospital stays compared to fluoroquinolones 2, 1
- For fully susceptible Salmonella typhi strains, fluoroquinolones (ciprofloxacin, ofloxacin) may be used, but resistance is increasingly common globally 2, 3
- Ciprofloxacin 500 mg twice daily for 7-10 days or ofloxacin 400 mg twice daily for 7-10 days can be effective when the organism is susceptible 3, 4
- Azithromycin has shown a 94% cure rate in children with typhoid fever and has a lower risk of relapse compared to ceftriaxone 1
Parenteral Therapy for Severe Cases
- For severe cases requiring hospitalization, ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days is recommended 2, 1
- Ceftriaxone has been shown to be effective for treatment of enteric fever with few adverse effects 5
- In a comparative study, ceftriaxone showed significant reduction in time to become afebrile, faster disappearance of clinical signs and symptoms, and shorter hospital stays compared to chloramphenicol 6
- Early studies showed that 5-8 days of ceftriaxone therapy was adequate for patients who were cured, with a mean period of defervescence of 4 days 7
Treatment Based on Resistance Patterns
- Local susceptibility patterns should guide therapy choice, as resistance patterns vary geographically and are changing over time 2, 3
- Over 70% of S. typhi isolates in many regions, particularly South Asia, are now resistant to fluoroquinolones, making ceftriaxone or azithromycin better empiric choices 1
- Extensively drug-resistant (XDR) strains of enteric fever have emerged in Pakistan that respond only to a limited number of antibiotics 8
- Consider travel history when selecting empiric therapy, particularly for cases originating from South Asia where fluoroquinolone resistance is high 3, 1
Monitoring and Response
- Obtain blood cultures before initiating antibiotics whenever possible 2, 3
- Monitor for clinical response, with expected fever clearance within 4-5 days of appropriate therapy 1
- Patients treated initially with parenteral antibiotics should be transferred to an oral regimen as soon as clinical improvement occurs and temperature has been normal for 24 hours 9
- For most patients with uncomplicated enteric fever, 7 days of appropriate antibiotics is recommended 9
Common Pitfalls to Avoid
- Avoid using ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 1
- Do not rely solely on clinical presentation for diagnosis; obtain cultures whenever possible 2, 1
- Recognize that short-course treatment with oral ofloxacin (5 days) has been shown to be significantly better than short-course ceftriaxone (3 days) in areas where the organism is susceptible 10
- Be aware that some patients may continue to carry the bacteria in their stool for a long time following treatment for the initial illness, potentially requiring longer courses of antibiotics to eradicate infection 8