Cefadroxil vs. Cephalexin: Practical Advantages
Cefadroxil's primary advantage over cephalexin is its longer half-life (1.61 hours vs. 1.10 hours), enabling twice-daily dosing instead of four-times-daily, which dramatically improves medication adherence while maintaining equivalent antibacterial activity against methicillin-susceptible Staphylococcus aureus (MSSA) and streptococci. 1, 2
Pharmacokinetic Superiority
Cefadroxil achieves a 46% longer serum half-life compared to cephalexin (1.61 hours vs. 1.10 hours), allowing sustained therapeutic concentrations with less frequent dosing 2.
Food intake does not affect cefadroxil absorption, whereas cephalexin absorption can be reduced when taken with meals, making cefadroxil more convenient for real-world administration 1.
Cefadroxil produces higher and more sustained tissue and fluid concentrations than cephalexin, potentially improving penetration into infected sites 1.
Dosing Convenience and Adherence
Cefadroxil requires only twice-daily dosing (40 mg/kg/dose, maximum 1,500 mg/dose) to achieve pharmacodynamic targets (fT>MIC ≥40% for MIC ≤4 mg/L), compared to cephalexin's three-to-four-times-daily requirement (25 mg/kg/dose, maximum 750 mg/dose) 2.
In pediatric pyoderma studies, 95% of patients taking once-daily cefadroxil completed 100% of their medication, compared to only 65% of patients taking twice-daily cephalexin (P<0.0001), demonstrating dramatically superior adherence 3.
In adult skin infections, only 2% of cefadroxil patients returned unused capsules, compared to 77% of cefaclor patients (a similar multi-dose regimen), highlighting the compliance advantage of less frequent dosing 4.
Equivalent or Superior Clinical Efficacy
Cefadroxil achieved 96% bacteriologic eradication in pediatric pyodermas versus 89% with cephalexin (P=0.042), with an overall effective response of 94% versus 86% (P=0.024), demonstrating statistically superior outcomes 3.
Both agents have identical MIC distributions against MSSA isolates (MIC₅₀ = 2 μg/mL, MIC₉₀ = 4 μg/mL), confirming equivalent in vitro potency despite the dosing difference 5.
Clinical cure rates are statistically equivalent when comparing cefadroxil once-daily to cephalexin four-times-daily regimens (91% vs. 95%, not significantly different), but the adherence benefit makes cefadroxil more reliable in outpatient settings 4.
Practical Clinical Algorithm
For uncomplicated skin and soft tissue infections (cellulitis, pyoderma) caused by MSSA or streptococci:
Choose cefadroxil 1,000 mg twice daily (adults) or 30-40 mg/kg/dose twice daily (pediatrics, maximum 1,500 mg/dose) for 5 days if clinical improvement occurs 1, 2.
Reserve cephalexin 500 mg four times daily (adults) or 25 mg/kg/dose three times daily (pediatrics, maximum 750 mg/dose) only when cefadroxil is unavailable or contraindicated 2.
Both agents are equally inappropriate for MRSA infections, requiring alternative therapy with trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or vancomycin 5.
Critical Caveats
Neither agent should be used for necrotizing infections, animal bites, or moderate-to-severe diabetic foot infections, which require broader polymicrobial coverage 1.
The longer half-life does not translate to once-daily dosing for serious infections; twice-daily cefadroxil is required to maintain adequate pharmacodynamic targets (fT>MIC ≥40%) 2.
Cefadroxil costs more than cephalexin, but the adherence benefit and reduced pill burden may offset this in outpatient settings where treatment failure from non-compliance is common 1, 3.
Both agents have higher MICs (2-4 μg/mL) than IV cephalosporins like cefazolin (MIC₅₀ 0.5 μg/mL), making them less suitable for severe infections requiring aggressive therapy 5.