What is the recommended dose of ceftriaxone (Ceftriaxone) for treating Salmonella Typhi?

Ceftriaxone Dosing for Salmonella Typhi

For typhoid fever caused by Salmonella Typhi, ceftriaxone should be dosed at 75 mg/kg/day (maximum 4 grams) given once daily for 5-7 days in children, or 3-4 grams once daily for 7 days in adults. 1, 2

Adult Dosing

• The standard adult dose is 3-4 grams IV or IM once daily for 7 days 2
• This regimen achieves rapid blood culture sterilization, with 100% of patients culture-negative by day 3 compared to 40% with chloramphenicol 1
• Clinical cure rates of 79-90% have been demonstrated with this short-course therapy 1, 2

Pediatric Dosing

• Children should receive 75 mg/kg/day (maximum 4 grams) IV or IM once daily for 5-7 days 1, 2
• Alternative dosing of 60-80 mg/kg/day has also been used successfully 3
• The once-daily dosing provides convenience and allows for potential outpatient management in stable patients 3

Treatment Duration Considerations

• A 5-day course is adequate for uncomplicated typhoid fever, with studies showing equivalent efficacy to 14 days of chloramphenicol 1
• Extend to 7 days for bacteremic patients or those with more severe disease 2
• Peak and trough ceftriaxone concentrations remain well above the MIC for S. Typhi throughout the dosing interval, supporting once-daily administration 4

Clinical Response Expectations

• Defervescence typically occurs within 4-7 days in uncomplicated cases 4, 2
• Blood cultures become negative significantly faster than with chloramphenicol (100% negative by day 3 vs. 40%) 1
• Some patients (approximately 20-30%) may experience prolonged fever beyond 7 days despite successful treatment 1, 2

Important Caveats

• Do not discontinue therapy prematurely if fever persists beyond 5 days, as prolonged fever does not indicate treatment failure and occurs in a subset of patients who ultimately achieve cure 1, 2
• Relapse rates are low (0-10%) with ceftriaxone compared to chloramphenicol 1, 3
• Monitor for emerging resistance: while all isolates in clinical trials were susceptible, some strains now show elevated MICs (up to 2 μg/mL), necessitating ongoing surveillance 5
• Ceftriaxone causes less bone marrow suppression than chloramphenicol, with significantly higher hematocrit and leukocyte counts at day 14 1

Alternative Considerations for Complicated Cases

• For patients with complications or treatment failure, fluoroquinolones remain first-line alternatives 6
• In HIV-infected patients with advanced disease (CD4+ <200), extend treatment to 2-6 weeks 6
• Azithromycin (MIC90 of 8 μg/mL) is a suitable oral alternative for community treatment 5