What is an alternative to Keflex (Cephalexin) for MSSA and Strep Pyo infections that requires less frequent dosing?

Alternative Antibiotics to Cephalexin for MSSA and Strep Pyogenes Infections with Less Frequent Dosing

For MSSA and Strep pyogenes infections, amoxicillin-clavulanate 875/125mg twice daily is the preferred alternative to cephalexin that requires less frequent dosing. 1

First-Line Options with Less Frequent Dosing

• Amoxicillin-clavulanate:

  • Dosing: 875/125mg twice daily (BID)
  • Benefits: Relatively broad-spectrum oral agent that includes anaerobic coverage 2
  • Effective against both MSSA and Strep pyogenes

• Cefadroxil:

  • Dosing: Can be given once or twice daily (compared to QID dosing for cephalexin)
  • Similar efficacy: MIC distributions for cefadroxil and cephalexin against MSSA are statistically equivalent (MIC50 values of 2 μg/mL and MIC90 values of 4 μg/mL) 3
  • Advantage: Slower clearance allowing for less frequent dosing compared to cephalexin

Alternative Options Based on Infection Severity

For Mild Infections:

• Levofloxacin:
  • Dosing: Once daily
  • Note: Suboptimal against S. aureus compared to other options 2

For Moderate to Severe Infections:

• Clindamycin:

  • Dosing: 300mg three times daily (TID)
  • Effective against both streptococcal and staphylococcal infections 1
  • Consider ordering a "D-test" before using for MRSA 2

• Linezolid:

  • Dosing: Twice daily
  • Highly effective for skin and soft tissue infections
  • Active against both MSSA and MRSA
  • Available in both oral and IV formulations 1

Clinical Considerations

Dosing Optimization

Recent research suggests that cephalexin itself could be given less frequently than the traditional QID dosing:

• For twice-daily (BID) dosing: 22-45 mg/kg for MSSA with MICs of 1-2 mg/L 4
• For thrice-daily (TID) dosing: 15-25 mg/kg for the same MIC range 4

Important Caveats

• Penicillin remains the drug of choice for pure streptococcal skin infections, but is not effective against MSSA 5
• Up to 10% of penicillin-allergic patients may also be allergic to cephalosporins 1
• Cephalosporins are contraindicated in patients with immediate (anaphylactic-type) hypersensitivity to penicillin 6
• Local antibiotic resistance patterns should be considered when selecting therapy 1

Monitoring and Follow-up

• Monitor for clinical improvement within 48-72 hours of starting the new antibiotic 1
• Duration of therapy typically ranges from 7-14 days based on clinical response and infection severity 1
• Consider culture and susceptibility testing before starting new antibiotics to guide therapy 1

Conclusion for Clinical Practice

When selecting an alternative to cephalexin for MSSA and Strep pyogenes infections that requires less frequent dosing, amoxicillin-clavulanate twice daily offers the best combination of efficacy, spectrum of coverage, and convenient dosing schedule. For patients with penicillin allergies, clindamycin three times daily or linezolid twice daily are appropriate alternatives.