Is Keflex (cephalexin) effective for treating Methicillin-resistant Staphylococcus aureus (MRSA) infections?

Keflex (Cephalexin) for MRSA Infections

Keflex (cephalexin) is not effective for treating methicillin-resistant Staphylococcus aureus (MRSA) infections and should not be used as monotherapy when MRSA is suspected or confirmed. 1

Rationale for Ineffectiveness Against MRSA

• Cephalexin is listed in treatment guidelines specifically for methicillin-susceptible Staphylococcus aureus (MSSA) infections, not for MRSA 1
• MRSA, by definition, is resistant to beta-lactam antibiotics including cephalexin and other first-generation cephalosporins 2
• The 2014 Infectious Diseases Society of America (IDSA) guidelines clearly separate treatment recommendations for MSSA and MRSA infections, with cephalexin only appearing in the MSSA treatment category 1

Recommended Antibiotics for MRSA Infections

For suspected or confirmed MRSA skin and soft tissue infections (SSTIs), the following antibiotics are recommended instead:

Oral Options:

• Trimethoprim-sulfamethoxazole (1-2 double-strength tablets twice daily) 1
• Clindamycin (300-450 mg four times daily) 1
• Doxycycline or minocycline (100 mg twice daily) 1
• Linezolid (600 mg twice daily) - more expensive option 1

Intravenous Options (for severe infections):

• Vancomycin (15-20 mg/kg/day in 2 divided doses) - parenteral drug of choice 1
• Daptomycin (4 mg/kg every 24 hours) 1
• Linezolid (600 mg every 12 hours) 1
• Ceftaroline (600 mg twice daily) 1

Clinical Evidence

• In a randomized controlled trial examining uncomplicated skin abscesses in a population at risk for MRSA, cephalexin showed no benefit over placebo after incision and drainage, with cure rates of 84.1% for cephalexin versus 90.5% for placebo 3
• A 2017 study comparing cephalexin alone versus cephalexin plus trimethoprim-sulfamethoxazole for uncomplicated cellulitis found no significant difference in clinical cure rates in the per-protocol analysis, though the modified intention-to-treat analysis suggested a possible benefit from adding anti-MRSA coverage 4
• Surveillance data indicates increasing resistance of MRSA to commonly prescribed antibiotics over time, highlighting the importance of appropriate antibiotic selection 5

Special Considerations

• Incision and drainage is the primary treatment for purulent skin infections (abscesses) and may be sufficient for uncomplicated cases without systemic symptoms 1
• Antibiotic therapy active against MRSA is recommended for patients with:
  • Systemic inflammatory response syndrome (SIRS) 1
  • Failed initial antibiotic treatment 1
  • Markedly impaired host defenses 1
  • Severe or rapidly progressing infections 1

Common Pitfalls to Avoid

• Misdiagnosis pitfall: Assuming all staphylococcal infections are methicillin-susceptible without obtaining cultures 1
• Treatment pitfall: Using cephalexin empirically when local MRSA prevalence is high 5
• Follow-up pitfall: Failing to reassess patients who don't improve within 48-72 hours of starting treatment 1

Algorithm for Management of Suspected Staphylococcal Skin Infections

1. Obtain cultures when possible before starting antibiotics 1
2. For purulent infections (abscesses):
   • Perform incision and drainage 1
   • If mild infection with no systemic symptoms: drainage alone may be sufficient 1
   • If moderate/severe or with systemic symptoms: add anti-MRSA antibiotic 1
3. For non-purulent cellulitis:
   • If no risk factors for MRSA: cephalexin is appropriate 1
   • If MRSA suspected or confirmed: use one of the recommended MRSA-active antibiotics 1
4. Reassess in 48-72 hours and adjust therapy based on culture results and clinical response 1

In conclusion, when treating skin and soft tissue infections in areas with significant MRSA prevalence, clinicians should either obtain cultures to guide therapy or empirically select antibiotics with activity against MRSA rather than relying on cephalexin alone.