Does Keflex (Cephalexin) cover Methicillin-resistant Staphylococcus aureus (MRSA)?

Keflex (Cephalexin) Does Not Cover MRSA

Keflex (cephalexin) is ineffective against MRSA infections and should not be used when MRSA is suspected or confirmed. According to the FDA drug label, methicillin-resistant staphylococci are explicitly listed as resistant to cephalosporins, including cephalexin 1.

Evidence Against Cephalexin for MRSA

The Infectious Diseases Society of America (IDSA) guidelines clearly categorize antibiotics for staphylococcal infections based on methicillin resistance:

• For methicillin-susceptible S. aureus (MSSA) infections:

  • Cephalexin is appropriate and recommended 2
  • Dosing: 500 mg orally four times daily for adults 2

• For methicillin-resistant S. aureus (MRSA) infections:

  • Vancomycin, linezolid, daptomycin, clindamycin, trimethoprim-sulfamethoxazole, doxycycline, or minocycline are recommended 2, 3
  • Cephalexin is specifically NOT recommended due to lack of activity 3

Mechanism of MRSA Resistance

MRSA carries the mecA gene which encodes an altered penicillin-binding protein (PBP2a) with significantly reduced affinity for beta-lactam antibiotics, including all cephalosporins 2, 3. This mechanism renders cephalexin and other cephalosporins ineffective against MRSA.

Clinical Evidence

Several clinical studies have examined cephalexin's efficacy against MRSA:

1. A randomized controlled trial by Chen et al. (2011) found that in patients with skin infections where 87.8% of S. aureus isolates were MRSA, cephalexin was no better than placebo (84.1% vs 90.5% cure rate) 4.

2. A 2014 study showed increasing resistance of MRSA to commonly prescribed antibiotics, including cephalexin, highlighting the importance of appropriate antibiotic selection 5.

Appropriate Alternatives for MRSA

For suspected or confirmed MRSA infections, the IDSA recommends:

• For mild-moderate skin and soft tissue infections:

  • Trimethoprim-sulfamethoxazole (1-2 double-strength tablets twice daily)
  • Doxycycline or minocycline (100 mg twice daily)
  • Clindamycin (300-450 mg three times daily) if susceptible
  • Linezolid (600 mg twice daily) 2, 3

• For severe infections:

  • Vancomycin (15-20 mg/kg/dose IV every 8-12 hours)
  • Linezolid (600 mg IV/PO twice daily)
  • Daptomycin (4-6 mg/kg/dose IV daily) 2, 3

Common Pitfalls in MRSA Treatment

1. Empiric treatment failure: Using cephalexin empirically when MRSA is suspected can lead to treatment failure and worsening infection.

2. Misinterpreting clinical improvement: Some studies show improvement with cephalexin in MRSA infections 6, 7, but this is likely due to adequate drainage procedures rather than antibiotic efficacy.

3. Inadequate cultures: Always obtain cultures before starting antibiotics when MRSA is suspected to guide appropriate therapy.

4. Overlooking drainage procedures: For purulent MRSA infections, incision and drainage is a critical component of treatment, sometimes more important than antibiotic choice 4.

In summary, while cephalexin remains an excellent choice for MSSA infections, it has no reliable activity against MRSA and should not be used when MRSA is suspected or confirmed. Appropriate alternatives with documented activity against MRSA should be selected based on infection severity, patient factors, and local resistance patterns.