What are the differences between cefadroxil and cephalexin for treating streptococcal infections?

Cefadroxil vs Cephalexin: Key Differences

Primary Recommendation

Both cefadroxil and cephalexin are equally effective first-generation cephalosporins for treating streptococcal infections in penicillin-allergic patients, but cefadroxil offers superior convenience with once-daily dosing compared to cephalexin's twice-daily regimen, which significantly improves medication compliance. 1, 2

Dosing Differences

• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 2, 3
• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 2, 4

The once-daily dosing of cefadroxil represents a major practical advantage, with studies demonstrating 95% of patients completing 100% of their medication versus only 65% with twice-daily cephalexin 5.

Pharmacokinetic Differences

• Cefadroxil exhibits a longer serum half-life and more sustained tissue concentrations than cephalexin, permitting less frequent dosing 6
• Cefadroxil is virtually unaffected by food intake, allowing administration during meals without compromising absorption, whereas cephalexin absorption may be more variable 6
• Both drugs achieve peak serum concentrations rapidly, with cefadroxil reaching approximately 16 mcg/mL after 500 mg and 28 mcg/mL after 1000 mg 3
• Over 90% of cefadroxil is excreted unchanged in urine within 24 hours, maintaining therapeutic concentrations well above the MIC of susceptible pathogens for 20-22 hours 3

Clinical Efficacy Comparison

• Bacteriologic eradication rates favor cefadroxil: 96% versus 89% for cephalexin in pediatric pyodermas (p = 0.042) 5
• Overall effective response is significantly higher with cefadroxil: 94% versus 86% for cephalexin (p = 0.024) 5
• For streptococcal tonsillopharyngitis specifically, both agents show equivalent bacteriologic cure rates (87% for cephalexin twice daily, 81% for cefadroxil once daily, p = 0.61) 7
• Clinical cure rates are comparable: 91% for cephalexin versus 84% for cefadroxil in tonsillopharyngitis 7

Guideline Positioning

• Both are classified as narrow-spectrum, first-generation cephalosporins and are preferred over broad-spectrum agents (cefuroxime, cefixime, cefdinir) for streptococcal infections 1
• The Infectious Diseases Society of America and American Academy of Pediatrics recommend either agent as first-line alternatives for penicillin-allergic patients without immediate/anaphylactic hypersensitivity 1, 2
• Neither should be used in patients with immediate penicillin hypersensitivity due to up to 10% cross-reactivity risk 1, 2

Compliance and Practical Considerations

• Cefadroxil's once-daily dosing dramatically improves compliance: This is the single most important clinical difference, as medication adherence directly impacts treatment success and prevention of complications like acute rheumatic fever 5
• Both require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus 2
• The suspension formulation of cephalexin is well-accepted by young children, though cefadroxil's less frequent dosing may offset this advantage 8

Safety Profile

• Both agents demonstrate similar safety profiles with mild and infrequent adverse events 9, 5
• No serious adverse reactions have been reported with either drug in comparative studies 9
• Both are generally well-tolerated in pediatric and adult populations 8, 5

Cost Considerations

When efficacy, palatability, and adverse reactions are similar between antibiotics, cost factors may influence selection, though specific pricing data varies by region and formulation 8.

Common Pitfalls to Avoid

• Do not use either agent in patients with immediate/anaphylactic penicillin reactions - the 10% cross-reactivity risk mandates use of clindamycin or azithromycin instead 1, 2
• Do not prescribe shorter courses than 10 days - even though symptoms resolve in 3-4 days, full course completion is essential for preventing acute rheumatic fever 2
• Do not assume food intake affects cefadroxil absorption - unlike some antibiotics, cefadroxil can be taken with meals, which may improve compliance 6
• Do not select broad-spectrum cephalosporins when these narrow-spectrum agents are appropriate - this unnecessarily increases antibiotic resistance risk 1