What is the preferred treatment between cefixime (Cephalosporin) and levofloxacin (Fluoroquinolone) for typhoid fever?

Ceftriaxone is Superior to Both Cefixime and Levofloxacin for Typhoid Fever Treatment

For typhoid fever treatment, ceftriaxone is the preferred first-line agent over both cefixime and levofloxacin due to high efficacy and lower resistance rates, particularly for patients from regions with high fluoroquinolone resistance. 1, 2

Current Resistance Patterns and First-Line Treatment

Antimicrobial resistance has significantly changed the treatment landscape for typhoid fever:

• More than 70% of Salmonella typhi isolates imported to the UK are resistant to fluoroquinolones, including levofloxacin 1
• All isolates reported to the UK Health Protection Agency were sensitive to ceftriaxone 1
• Fluoroquinolone resistance is particularly high in South and Southeast Asia 2
• WHO guidelines recommend ceftriaxone as a first-line option for empiric treatment of typhoid fever 1

Treatment Algorithm Based on Clinical Presentation

For Severe or Complicated Cases:

• First choice: Ceftriaxone IV 50-80 mg/kg/day (maximum 2g/day) for 7-10 days 2
• Alternative: Azithromycin (if ceftriaxone unavailable)

For Uncomplicated Cases with Oral Therapy Option:

1. First choice: Azithromycin 20mg/kg/day (maximum 1g/day) for 7 days 1, 2
2. Second choice: Cefixime 20mg/kg/day in two divided doses (maximum 400mg twice daily) for 7 days 2
3. Third choice: Fluoroquinolones (only if susceptibility is confirmed) 1, 2

Comparative Efficacy

Cefixime vs. Levofloxacin:

• Cefixime has reported treatment failure rates of 4-37.6% 1
• Cefixime may not perform as well as fluoroquinolones based on clinical trials 3
• Levofloxacin has shown efficacy in small studies but is limited by increasing resistance 4, 5

Ceftriaxone vs. Fluoroquinolones:

• Ceftriaxone is preferred over fluoroquinolones due to increasing resistance to the latter 1, 2
• Ceftriaxone has excellent activity against multidrug-resistant strains 6

Azithromycin Considerations:

• Azithromycin has shown lower risk of clinical failure compared to fluoroquinolones 1
• Azithromycin is particularly useful for quinolone-resistant strains 2
• Relapse rates for azithromycin (<3%) are lower than ceftriaxone (<8%) 1

Treatment Duration and Response

• Treatment should continue for 14 days to reduce risk of relapse 1
• Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy 2
• Fever clearance time is typically <4 days with appropriate treatment 1

Important Caveats and Pitfalls

1. Resistance Testing Pitfall: Using ciprofloxacin discs alone to determine Salmonella typhi sensitivity is unreliable. The organism should also be sensitive to nalidixic acid on disc testing to be considered sensitive to fluoroquinolones 1

2. Diagnostic Pitfall: The serological Widal test lacks sensitivity and specificity and is not recommended for diagnosis 1

3. Treatment Duration Pitfall: Stopping treatment early when symptoms resolve can lead to relapse; complete the full course 2

4. Empiric Treatment Pitfall: Starting empiric treatment without obtaining blood cultures can miss the opportunity to confirm diagnosis and determine antibiotic susceptibility 2

5. Resistance Evolution: Resistance patterns continue to evolve, making it essential to consider local resistance patterns when selecting therapy 2

In conclusion, while both cefixime and levofloxacin have been used to treat typhoid fever, current evidence and guidelines strongly favor ceftriaxone as the preferred parenteral agent and azithromycin as the preferred oral agent due to increasing fluoroquinolone resistance worldwide.