Oral Equivalent to Cefazolin
Cephalexin is the standard oral equivalent to intravenous cefazolin, with both being first-generation cephalosporins that provide comparable coverage against methicillin-susceptible Staphylococcus aureus and streptococcal infections. 1
Primary Oral Alternative
- Cephalexin (500 mg orally 3-4 times daily) is the most widely recommended oral first-generation cephalosporin and serves as the direct oral equivalent to cefazolin 1, 2
- Multiple guidelines from the American Heart Association and other societies recommend cephalexin for the same clinical indications where cefazolin would be used intravenously, including skin and soft tissue infections, urinary tract infections, and surgical prophylaxis 1
- A 2018 randomized controlled trial demonstrated that cephalexin 500 mg four times daily was non-inferior to intravenous cefazolin 2g daily (with probenecid) for uncomplicated mild-moderate skin and soft tissue infections, with failure rates of 4.2% vs 6.1% respectively 2
Secondary Oral Alternative
- Cefadroxil (500 mg orally twice daily) is an equally effective alternative with the advantage of less frequent dosing due to its longer half-life 3, 4
- Cefadroxil and cephalexin demonstrate statistically equivalent MIC distributions against MSSA isolates (both with MIC50 of 2 μg/mL and MIC90 of 4 μg/mL), suggesting similar in vitro antibacterial activity 3
- Clinical trials show comparable efficacy between cefadroxil and cephalexin for skin and soft tissue infections, with satisfactory clinical outcomes in 94% vs 89% of patients respectively 5
Clinical Applications Where Oral Equivalents Apply
- Skin and soft tissue infections: Both cephalexin and cefadroxil achieve cure rates of 90% or higher for streptococcal and staphylococcal infections 6, 7
- Urinary tract infections: Cephalexin 500 mg twice or thrice daily serves as a fluoroquinolone-sparing alternative for non-ESBL Enterobacteriaceae 4
- Endocarditis prophylaxis: Cephalexin 2g orally (50 mg/kg in children) is recommended as an alternative in penicillin-allergic patients for dental procedures 6, 1
- Step-down therapy: Oral cephalexin is the recommended switch from parenteral cefazolin when transitioning from IV to oral therapy 6
Important Caveats
- Cross-reactivity warning: Cephalosporins should NOT be used in patients with a history of anaphylaxis, angioedema, or urticaria to penicillins or ampicillin due to potential cross-reactivity 6, 1
- Resistance considerations: While cephalexin remains effective, some studies report high resistance rates among viridans group streptococci, which should be considered in specific clinical contexts 1
- Not equivalent for all indications: For severe infections requiring broad gram-negative coverage (where ceftriaxone or cefotaxime would be preferred over cefazolin), oral cephalosporins are NOT appropriate equivalents 6
- Dosing frequency matters: Cephalexin requires 3-4 times daily dosing for optimal efficacy, while cefadroxil's twice-daily dosing may improve compliance 3, 4