What is the difference between Keflex (cephalexin) and Duricef (cefadroxil) in treating infections?

Keflex vs Duricef: Key Differences and Clinical Considerations

Both Keflex (cephalexin) and Duricef (cefadroxil) are first-generation cephalosporins with equivalent antibacterial activity against methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pyogenes, but cefadroxil offers the advantage of once-daily dosing due to its longer half-life, while cephalexin requires twice-daily to four-times-daily administration. 1, 2, 3

Antibacterial Spectrum and Potency

• Both agents have identical MIC distributions against MSSA isolates, with MIC50 values of 2 μg/mL and MIC90 values of 4 μg/mL, demonstrating statistically equivalent in vitro activity 3
• Both drugs effectively cover gram-positive cocci including Staphylococcus aureus (MSSA only), Staphylococcus epidermidis, and Streptococcus pyogenes 4, 5
• First-generation cephalosporins like cephalexin and cefadroxil have poor coverage for Haemophilus influenzae and should not be used when this pathogen is suspected 1
• Neither agent has activity against methicillin-resistant Staphylococcus aureus (MRSA), anaerobes, or atypical organisms 1, 5

Dosing and Administration

Cefadroxil:

• 30 mg/kg once daily (maximum 1 gram) for 10 days 1
• Single daily dosing significantly improves medication compliance, with 95% of patients completing 100% of prescribed doses 2

Cephalexin:

• Children: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1
• Adults: 250 mg four times daily or 500 mg twice daily 1
• More frequent dosing (2-4 times daily) results in lower compliance rates, with only 65% of patients taking 100% of prescribed medication 2

Clinical Efficacy Data

Skin and Soft Tissue Infections

• In a head-to-head pediatric pyoderma study, cefadroxil demonstrated superior bacteriologic eradication (96% vs 89%, p=0.042) and overall effective response (94% vs 86%, p=0.024) compared to cephalexin 2
• Clinical cure rates for uncomplicated skin infections are comparable: cephalexin achieved 89-97% cure rates across multiple studies 6, 4
• Both agents maintain cure rates of 90% or higher for streptococcal and staphylococcal skin infections 5

Group A Streptococcal Pharyngitis

• Both cephalexin and cefadroxil are IDSA-recommended alternatives for penicillin-allergic patients (avoiding those with immediate hypersensitivity) 1
• Both carry a "Strong, high" recommendation strength for this indication 1
• Standard 10-day treatment duration is required for both agents 1

Practical Clinical Considerations

Choose cefadroxil when:

• Medication compliance is a concern, as once-daily dosing significantly improves adherence (95% vs 65% completion rates) 2
• Treating pediatric patients where simplified dosing schedules are advantageous 2
• Cost is not prohibitive and convenience is prioritized 5

Choose cephalexin when:

• Cost considerations are paramount, as cephalexin is generally less expensive 5
• Cefadroxil is unavailable or not formulary-approved 1
• Patient has established tolerance to cephalexin 5

Safety and Tolerability

• Both agents are well-tolerated with similar adverse event profiles 4, 2
• Gastrointestinal side effects (diarrhea, nausea) are the most common adverse events for both drugs 6, 4
• Cephalexin suspension is well-accepted by young children 5
• No significant differences in drug-related adverse events between the two agents 4, 2

Common Pitfalls to Avoid

• Do not use either agent for infections likely involving H. influenzae (such as acute bacterial rhinosinusitis), as first-generation cephalosporins have inadequate activity against this pathogen 1
• Avoid in patients with immediate hypersensitivity to penicillin (anaphylaxis, angioedema), as cross-reactivity risk exists 1
• Do not rely on either agent for MRSA coverage, despite occasional clinical responses seen in studies where incision and drainage likely contributed to outcomes 6
• Do not use for infections requiring anaerobic coverage (intra-abdominal, diabetic foot infections), as neither agent has anaerobic activity 1

Bottom Line Algorithm

For mild-to-moderate MSSA or streptococcal skin/soft tissue infections or Group A strep pharyngitis in penicillin-allergic patients:

1. First choice: Cefadroxil 30 mg/kg once daily (max 1g) × 10 days if compliance is a concern or convenience is prioritized 1, 2

2. Alternative: Cephalexin 20 mg/kg twice daily (max 500mg per dose) × 10 days if cost is the primary consideration 1, 5

Both achieve equivalent clinical and bacteriologic outcomes, but cefadroxil's once-daily dosing provides a meaningful adherence advantage 2, 3