Cefuroxime for Typhoid Fever
Cefuroxime is NOT recommended for the treatment of typhoid fever (Salmonella Typhi infection) because it has inferior activity against S. Typhi compared to third-generation cephalosporins and is not included in any current treatment guidelines for this indication.
Why Cefuroxime Should Be Avoided
Cefuroxime is a second-generation cephalosporin with significantly weaker activity against S. pneumoniae and other pathogens compared to third-generation agents, and this reduced potency extends to Salmonella species. 1
- The activity of cefuroxime against S. pneumoniae cannot be predicted by susceptibility testing of third-generation cephalosporins like cefotaxime or ceftriaxone, indicating it is a distinctly less potent agent 1
- While cefuroxime has some in vitro activity against Salmonella species 2, there is only one small, dated study (1996) showing clinical efficacy in 30 patients with typhoid fever 3
- No current guidelines from the WHO, American Academy of Pediatrics, or Infectious Diseases Society of America recommend cefuroxime for typhoid fever 4, 5, 6
Recommended First-Line Treatment Instead
Azithromycin 500 mg once daily for 7 days (or 20 mg/kg/day in children, maximum 1g/day) is the preferred first-line treatment for uncomplicated typhoid fever, particularly in areas with high fluoroquinolone resistance. 4, 5, 6
Evidence Supporting Azithromycin Over Other Options:
- Azithromycin demonstrates a 52% reduction in clinical failure compared to fluoroquinolones (OR 0.48,95% CI 0.26-0.89) 4, 6
- Hospital stay is shortened by approximately 1 day compared to fluoroquinolones (mean difference -1.04 days) 4, 6
- Relapse risk is dramatically lower with azithromycin versus ceftriaxone (OR 0.09,95% CI 0.01-0.70) 4, 6
- Cure rate reaches 94% in children with typhoid fever 5, 6
Alternative Treatment Options (When Azithromycin Cannot Be Used)
If azithromycin is contraindicated or unavailable, use ceftriaxone 1-2g IV/IM daily for 5-7 days in adults (50-80 mg/kg/day in children, maximum 2g/day), NOT cefuroxime. 4, 5
Third-Generation Cephalosporins (Acceptable Alternatives):
- Ceftriaxone has documented cure rates of 23 of 25 patients (92%) with typhoid fever and a 4% relapse rate 7
- Cefotaxime cured 50 of 61 patients (82%) with typhoid/paratyphoid fever with a 6% relapse rate 7
- Cefixime (oral option) 400 mg daily for 7 days is listed as an alternative, though it has documented treatment failure rates of 4-37.6% and requires mandatory test-of-cure at 1 week 4, 5
Fluoroquinolones (Only When Susceptibility Confirmed):
- Ciprofloxacin or ofloxacin may be used ONLY when culture confirms susceptibility 4, 5
- Avoid empiric fluoroquinolone use for cases from South or Southeast Asia where resistance exceeds 70-96% 1, 4, 5
Critical Clinical Pitfalls to Avoid
- Never use cefuroxime when third-generation cephalosporins are available - the inferior activity may lead to treatment failure 1
- Do not use ciprofloxacin empirically for travel-associated cases from South Asia - resistance rates approach 96% in some regions 4
- Obtain blood cultures before starting antibiotics whenever possible - they have the highest yield within the first week of symptoms 4, 5
- Complete the full 7-day course even if fever resolves early - premature discontinuation increases relapse risk to 10-15% 4
Expected Clinical Response
- Fever should clear within 4-5 days of appropriate therapy 4, 5, 6
- If no improvement by day 5, consider resistance or alternative diagnosis 4, 6
- Monitor for intestinal perforation, which occurs in 10-15% of patients with illness duration exceeding 2 weeks 4, 6