What is the difference between cefadroxil (Cefadroxil) and cefixime (Cefixime) in treating bacterial infections?

Cefadroxil vs Cefixime: Key Differences in Bacterial Coverage and Clinical Use

Cefadroxil and cefixime target opposite ends of the bacterial spectrum and are not interchangeable—cefadroxil is a first-generation cephalosporin effective against gram-positive organisms (streptococci and staphylococci) but has poor gram-negative and beta-lactamase coverage, while cefixime is a third-generation cephalosporin with potent activity against gram-negative bacteria (especially H. influenzae) but limited gram-positive coverage and no activity against staphylococci. 1

Spectrum of Activity: The Critical Distinction

Cefadroxil (First-Generation)

• Gram-positive coverage: Good activity against Streptococcus pyogenes, penicillin-susceptible S. pneumoniae, and methicillin-susceptible Staphylococcus aureus 1, 2
• Gram-negative coverage: Poor activity against Haemophilus influenzae and most Enterobacteriaceae 1
• Beta-lactamase stability: Easily hydrolyzed by beta-lactamases, making it ineffective against beta-lactamase-producing organisms 1
• Anaerobic coverage: Minimal to none 1

Cefixime (Third-Generation)

• Gram-negative coverage: Potent activity against H. influenzae (including beta-lactamase-producing strains), Neisseria gonorrhoeae, and most Enterobacteriaceae 3, 1, 4
• Gram-positive coverage: Limited activity against penicillin-susceptible S. pneumoniae only; may occasionally fail even against susceptible strains 3, 1
• No staphylococcal activity: Completely inactive against S. aureus 3, 1, 4
• No DRSP coverage: No clinically significant activity against drug-resistant S. pneumoniae 3, 1
• No anaerobic coverage: Inactive against Bacteroides fragilis 1

Clinical Indications: When to Use Each

Choose Cefadroxil For:

• Skin and soft tissue infections caused by streptococci or methicillin-susceptible staphylococci (community-acquired, non-MRSA) 1
• Pharyngitis/tonsillitis due to S. pyogenes 1
• Simple urinary tract infections in areas with low E. coli resistance 1
• Key requirement: No concern for beta-lactamase-producing organisms and no gram-negative pathogen involvement expected 1

Choose Cefixime For:

• Acute bacterial rhinosinusitis when H. influenzae is suspected, though limited pneumococcal coverage is a concern 3, 1
• Uncomplicated urinary tract infections 5
• Otitis media (though clinical response to S. pneumoniae is approximately 10% lower than comparators) 3, 5
• Uncomplicated gonorrhea (cervical/urethral) 5, 4
• Key requirement: H. influenzae confirmed or suspected, but adequate gram-positive coverage is not needed 1

Critical Clinical Pitfalls to Avoid

Never Use Cefadroxil For:

• Infections involving H. influenzae (respiratory tract infections, otitis media) 1
• Beta-lactamase-producing organisms 1

Never Use Cefixime For:

• Empiric community-acquired pneumonia (inadequate S. pneumoniae coverage, especially DRSP) 3, 1
• Staphylococcal infections (skin/soft tissue, bacteremia) 3, 1
• Anaerobic infections (Bacteroides fragilis) 1
• Enterococcal infections 1

Pharmacokinetic Advantages

• Cefixime: 3-hour elimination half-life permits once- or twice-daily dosing, potentially improving compliance 4, 6
• Cefadroxil: Slower clearance than cephalexin, allowing less frequent dosing 7

Comparative Efficacy Data

• In otitis media trials, cefixime 8 mg/kg daily achieved 74-81% bacteriological eradication rates, comparable to cefaclor and amoxicillin 5, 4
• However, S. pneumoniae response to cefixime was approximately 10% lower than active controls (69-82% vs 82%), while H. influenzae response was 7% higher 5
• Cefadroxil achieved 94% satisfactory clinical outcomes in skin/skin structure infections, comparable to cephalexin (89%) and cefuroxime axetil (97%) 2

The Bottom Line Algorithm

Never substitute one for the other—they address opposite bacterial spectrums 1:

1. If gram-positive coverage needed (strep throat, cellulitis, simple skin infections): Use cefadroxil 1
2. If gram-negative coverage needed (H. influenzae sinusitis, UTI with known gram-negative pathogen): Use cefixime 1
3. If both gram-positive AND gram-negative coverage needed: Neither drug is appropriate; consider amoxicillin-clavulanate or a respiratory fluoroquinolone 3