Ceftriaxone Duration for Enteric Fever: 14 Days

For enteric fever (typhoid and paratyphoid), ceftriaxone should be administered for 14 days to minimize relapse risk to less than 8%. 1

Evidence-Based Treatment Protocol

The UK guideline explicitly recommends 14 days of ceftriaxone treatment for enteric fever caused by Salmonella typhi and Salmonella paratyphi to reduce relapse risk. 1
This 14-day duration is significantly longer than the FDA-labeled "usual duration" of 4-14 days for general infections, reflecting the specific requirements of enteric fever treatment. 2

Adults should receive ceftriaxone 2-4 grams daily, typically administered as 2 grams once daily or 1 gram twice daily. 2
The FDA label specifies that the usual adult daily dose is 1-2 grams given once daily or in equally divided doses twice daily, with a maximum of 4 grams daily. 2
For severe cases or complicated infections, the higher end of the dosing range (2 grams daily) is appropriate. 2

Relapse rates with ceftriaxone are less than 8% when 14-day courses are used, compared to higher rates with shorter durations. 1
Relapsed enteric fever carries increased risk of serious complications including intestinal perforation, encephalopathy, and death. 1
In a Japanese cohort study, patients treated with ceftriaxone monotherapy had an 11% relapse rate, with relapses characterized by longer time to defervescence (>7 days after treatment initiation). 3

Start ceftriaxone immediately for suspected enteric fever, particularly in patients returning from Asia where >70% of isolates are fluoroquinolone-resistant. 1
Continue treatment for a minimum of 14 days total, regardless of clinical improvement. 1
If fever persists >7 days after treatment initiation, consider switching to a fluoroquinolone (if susceptible) or extending ceftriaxone duration beyond 14 days. 3
For patients who defervesce slowly (>7 days), continue ceftriaxone for at least 4 days after defervescence to prevent relapse. 3

Do not use 3-day ceftriaxone regimens for enteric fever. A Vietnamese study showed that 3 days of ceftriaxone resulted in 6 acute treatment failures and 1 relapse among 25 patients (28% failure rate), compared to 100% cure with 5 days of ofloxacin. 4
Even 5-7 day courses, while showing some efficacy in older studies, are associated with higher relapse rates than the recommended 14-day duration. 5, 6

Longer time to treatment initiation is a significant risk factor for relapse. 3
Begin empirical ceftriaxone therapy promptly in patients with suspected enteric fever, especially those with travel history to endemic areas. 1

If azithromycin is used instead of ceftriaxone, it should also be continued for 14 days, with relapse rates <3%. 1
Fluoroquinolones (when susceptible) have relapse rates <4% and faster fever clearance (<4 days), but resistance now exceeds 70% in Asian isolates. 1
Ampicillin and chloramphenicol show excellent susceptibility (91-94%) in recent Asian studies and may be reconsidered as alternatives, though traditional 12-14 day courses are required. 3

Expect defervescence within 4-7 days in uncomplicated cases. 6, 4
If fever persists beyond 7 days, reassess for complications, treatment failure, or alternative diagnoses. 3
Monitor patients for 1-2 months post-treatment to detect relapses, which typically occur within this timeframe. 6