What is the oral equivalent to cefazolin (Ancef)?

Oral Equivalent to Cefazolin

Cephalexin is the standard oral first-generation cephalosporin equivalent to cefazolin, with cefadroxil as an alternative option offering less frequent dosing. 1, 2

Primary Oral Alternatives

Cephalexin (first choice):

• Standard dosing: 500 mg orally 3-4 times daily for adults 3
• Pediatric dosing: 75-100 mg/kg/day divided into 3-4 doses 4
• Widely available as generic medication, relatively inexpensive, and recommended across multiple guidelines for skin/soft tissue infections, urinary tract infections, and as alternative therapy for streptococcal pharyngitis 1
• Available as capsules, tablets, and oral suspension formulations 2

Cefadroxil (alternative with convenience advantage):

• Standard dosing: 500 mg orally twice daily 5, 6
• Offers slower clearance allowing less frequent dosing compared to cephalexin 7
• Demonstrates equivalent MIC distributions to cephalexin (MIC50 of 2 μg/mL, MIC90 of 4 μg/mL) against methicillin-susceptible Staphylococcus aureus 7
• Clinical efficacy comparable to cephalexin in skin/soft tissue infections (94% vs 89% satisfactory outcomes) 6

Clinical Equivalence Evidence

Non-inferiority data:

• A randomized controlled trial demonstrated cephalexin 500 mg four times daily was non-inferior to cefazolin 2 g IV daily plus probenecid for uncomplicated mild-moderate skin/soft tissue infections 3
• Failure rates at 72 hours were similar: 4.2% for cephalexin vs 6.1% for cefazolin (risk difference 1.9%, 95% CI -3.7% to 7.6%) 3
• Clinical cure at 7 days: 100% for cephalexin vs 97.7% for cefazolin 3

Important Caveats and Limitations

Cross-reactivity concerns:

• Cephalosporins should NOT be used in patients with history of anaphylaxis, angioedema, or urticaria to penicillins or ampicillin due to potential cross-reactivity 4, 1

Resistance considerations:

• Studies show high resistance rates (96%) of viridans group streptococci to cephalexin, though ceftriaxone demonstrates 2-4 times more activity than cefazolin 4
• Both cephalexin and cefadroxil have higher MICs (2-4 μg/mL) compared to IV cefazolin (MIC50 0.5 μg/mL) against MSSA 7

Spectrum limitations:

• First-generation cephalosporins have narrower spectrum than cefazolin for certain indications 4
• For serious infections requiring parenteral cefazolin (e.g., surgical prophylaxis, endocarditis), oral cephalosporins are NOT appropriate substitutes during the acute phase 4

Practical Dosing Recommendations

For step-down therapy from IV cefazolin:

• Cephalexin 500 mg orally 3-4 times daily (preferred for most situations) 3
• Cefadroxil 500 mg orally twice daily (when adherence concerns favor less frequent dosing) 5, 6

Duration:

• Typically 7-10 days depending on infection type and clinical response 3, 6