What are the differences between cefuroxime and cefixime?

Key Differences Between Cefuroxime and Cefixime

Direct Answer

Cefuroxime is superior to cefixime for most respiratory infections because cefixime has poor activity against Streptococcus pneumoniae (especially penicillin-resistant strains) and should not be used for acute bacterial sinusitis, while cefuroxime provides significantly enhanced activity against β-lactamase-producing H. influenzae, M. catarrhalis, and S. pneumoniae. 1

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Generation and Spectrum Classification

Cefuroxime (Second-Generation)

• Broad-spectrum activity against both gram-positive and gram-negative organisms 2
• Excellent coverage of S. pneumoniae, H. influenzae, M. catarrhalis, and methicillin-susceptible S. aureus 3
• Achieves 75-85% coverage of S. pneumoniae and 70-85% coverage of H. influenzae based on pharmacokinetic/pharmacodynamic breakpoints 3
• Significantly enhanced activity against β-lactamase-producing organisms 1

Cefixime (Third-Generation)

• Despite being "third-generation," has poor activity against S. pneumoniae and is especially ineffective against penicillin-resistant strains 1
• Particularly active against Enterobacteriaceae, H. influenzae, and M. catarrhalis 4
• Little to no activity against S. aureus 4, 5
• Resistant to hydrolysis by many β-lactamases 4

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Critical Clinical Guideline Recommendation

The 2005 Journal of Allergy and Clinical Immunology practice parameter explicitly states that cefixime should NOT be used for acute bacterial sinusitis due to poor pneumococcal coverage. 1 This is a firm contraindication based on its ineffectiveness against the most common respiratory pathogen.

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Specific Pathogen Coverage Comparison

Streptococcus pneumoniae (Most Critical Difference)

• Cefuroxime: Adequate coverage (~75-85%), though limited against drug-resistant strains 3
• Cefixime: Poor coverage overall; essentially ineffective against penicillin-resistant strains 1
• Clinical implication: This single difference makes cefixime unsuitable for empiric respiratory tract infections 1

Haemophilus influenzae

• Cefuroxime: 70-85% coverage of β-lactamase-producing strains 3
• Cefixime: Excellent activity, including β-lactamase producers 4, 6

Moraxella catarrhalis

• Cefuroxime: ~50% coverage 3
• Cefixime: Excellent activity 4, 6

Staphylococcus aureus

• Cefuroxime: Excellent activity against methicillin-susceptible strains 3, 2
• Cefixime: Little to no clinically meaningful activity 4, 5, 7

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Dosing Convenience and Palatability

Dosing Schedule

• Cefuroxime: Twice-daily administration 1
• Cefixime: Once or twice-daily administration due to 3-hour half-life (vs. 1.5 hours for cefuroxime) 4, 6

Pediatric Palatability (Critical for Adherence)

• Cefuroxime axetil suspension: Unpalatable, which compromises medication adherence in children 1, 8
• Cefixime: Better tolerated than cefuroxime suspension, though gastrointestinal side effects (diarrhea) occur in up to 20% of patients 5
• Alternative consideration: If palatability is a major concern with cefuroxime, cefdinir suspension is "very well accepted" by children 8

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Approved Clinical Indications

Cefuroxime

• Acute and chronic sinusitis (specifically recommended by French and European guidelines) 3
• Respiratory tract infections 2
• Urinary tract infections 2
• Soft tissue infections 2
• Gonorrhea (parenteral form only) 3
• Central nervous system infections 2

Cefixime

• NOT for acute bacterial sinusitis 1
• Uncomplicated urinary tract infections 4
• Acute otitis media 4
• Upper and lower respiratory tract infections (only when S. pneumoniae is not suspected) 6
• Pharyngitis/tonsillitis 4

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Common Pitfalls to Avoid

Do NOT Use Cefixime When:

• Treating empiric respiratory infections where S. pneumoniae is a likely pathogen 1
• Managing acute bacterial sinusitis 1
• Staphylococcal coverage is needed 4, 5

Do NOT Assume Third-Generation = Better:

• Cefixime's "third-generation" classification does NOT translate to superior coverage for respiratory pathogens compared to cefuroxime 1
• The generation number reflects chemical structure, not clinical superiority for all indications 1

Palatability Matters in Pediatrics:

• If prescribing cefuroxime suspension to children, warn families about poor taste and consider alternatives like cefdinir if adherence becomes an issue 8

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Algorithmic Decision Framework

For Respiratory Tract Infections (Sinusitis, Pneumonia, Bronchitis):

1. First choice: Cefuroxime (covers S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus) 1, 3
2. Never use: Cefixime (inadequate pneumococcal coverage) 1
3. If cefuroxime suspension refused by child: Switch to cefdinir suspension 8

For Uncomplicated UTI or Otitis Media (When S. pneumoniae Less Likely):

1. Cefixime is acceptable due to excellent gram-negative coverage and once-daily dosing 4
2. Cefuroxime also effective but requires twice-daily dosing 1

For Skin/Soft Tissue Infections Requiring Staphylococcal Coverage:

1. Use cefuroxime (excellent anti-staphylococcal activity) 3, 2
2. Avoid cefixime (poor staphylococcal coverage) 4, 5

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Adverse Effect Profile

Cefuroxime

• Relatively free of serious side effects 2
• Metabolically stable with renal excretion 2
• Potential for superinfections with Pseudomonas or enterococci 2

Cefixime

• Diarrhea and stool changes most common (up to 20% of patients), usually mild and transient 5
• Cases of pseudomembranous colitis reported 6
• Generally well-tolerated overall 4