Is Cefadroxil (Cefadroxil) 1000mg twice daily (bid) equivalent to Keflex (Cephalexin)?

Cefadroxil 1000mg BID as an Alternative to Cephalexin

Cefadroxil 1000 mg twice daily is therapeutically equivalent to cephalexin (Keflex) 500 mg four times daily for treating methicillin-susceptible staphylococcal and streptococcal infections, with the advantage of less frequent dosing that improves compliance. 1

Pharmacologic Equivalence

Antimicrobial Activity

• Both cefadroxil and cephalexin demonstrate identical in vitro activity against MSSA, with MIC50 values of 2 μg/mL and MIC90 values of 4 μg/mL, indicating statistically equivalent antimicrobial potency 2
• Both agents are active against the same spectrum of organisms: beta-hemolytic streptococci, methicillin-susceptible staphylococci (including penicillinase-producing strains), Streptococcus pneumoniae, E. coli, Proteus mirabilis, and Klebsiella species 3, 4
• Neither agent has activity against MRSA, most enterococci, Pseudomonas, or Acinetobacter species 3, 4

Pharmacokinetic Advantages of Cefadroxil

• Cefadroxil has a longer serum half-life than cephalexin, allowing for twice-daily dosing versus four-times-daily dosing 5
• Peak serum concentrations after cefadroxil 1000 mg are approximately 28 mcg/mL, with measurable levels present 12 hours after administration 3
• Cefadroxil absorption is virtually unaffected by food intake, unlike cephalexin, permitting administration during meals 5
• Over 90% of cefadroxil is excreted unchanged in urine within 24 hours, with urinary concentrations maintained well above MIC for 20-22 hours after a 1-gram dose 3

Clinical Evidence of Equivalence

Direct Comparative Studies

• In urinary tract infections, cefadroxil 1000 mg twice daily achieved cure rates equivalent to cephalexin 500 mg four times daily (all but 1 patient cured in both groups) 6
• In odontogenic facial cellulitis, cefadroxil 1 gram daily achieved 100% cure rate versus 98% with cephalexin 250 mg four times daily, demonstrating therapeutic equivalence 7
• Multiple studies have established efficacy of once- or twice-daily cefadroxil compared with four-times-daily cephalexin regimens for respiratory tract, urinary tract, skin and soft tissue, and bone/joint infections 5

Guideline Recognition

• The IDSA Prosthetic Joint Infection Guidelines explicitly list cefadroxil 500 mg twice daily as an alternative to cephalexin 500 mg three or four times daily for chronic oral antimicrobial suppression of oxacillin-susceptible staphylococci 1
• This guideline placement confirms regulatory and expert consensus that these agents are interchangeable for staphylococcal infections 1

Dosing Equivalence

Standard Regimens

• Cephalexin standard dosing: 500 mg three to four times daily for skin and soft tissue infections 1, 8
• Cefadroxil equivalent dosing: 500 mg twice daily or 1000 mg twice daily 1, 3
• For serious infections requiring higher cephalexin doses (500 mg QID = 2000 mg/day), cefadroxil 1000 mg BID (2000 mg/day) provides equivalent total daily dose with superior pharmacokinetics 3, 5

Clinical Advantages of Cefadroxil

Compliance Benefits

• Twice-daily dosing significantly improves patient compliance compared to four-times-daily regimens, which is critical for successful outpatient infection management 5
• Administration during meals is possible without affecting absorption, further enhancing convenience 5

Safety Profile

• Adverse reactions are minimal and comparable between agents, with only 2 cefadroxil-treated patients versus 1 cephalexin-treated patient experiencing adverse effects in comparative trials 7
• Both require dose adjustment for renal impairment 1

Important Caveats

When NOT to Use Either Agent

• Neither cefadroxil nor cephalexin should be used for MRSA infections; alternative agents (vancomycin, linezolid, daptomycin, clindamycin, or TMP-SMX) are required 1
• Patients with immediate hypersensitivity reactions to penicillins should avoid both agents due to cross-reactivity risk 1, 8
• Both have limited activity against Pasteurella multocida and anaerobes, requiring alternative coverage for animal bites or anaerobic infections 8

Susceptibility Testing Considerations

• Modern cefazolin-cephalexin surrogate testing (per CLSI/USCAST) has recategorized many isolates from resistant to susceptible, expanding the utility of both agents 9
• Direct susceptibility testing should guide therapy when available, though both agents share similar susceptibility patterns 2, 9

Practical Prescribing

• For uncomplicated lower urinary tract infections, cephalexin 500 mg twice or three times daily is now considered equivalent to traditional four-times-daily dosing, making it comparable to cefadroxil 500 mg twice daily 9
• For more serious infections (e.g., musculoskeletal infections), the higher dose of cefadroxil 1000 mg BID provides sustained therapeutic levels with convenient dosing 2, 5