Does cephalexin (a first-generation cephalosporin) cover Methicillin-resistant Staphylococcus aureus (MRSA)?

Cephalexin Does Not Cover MRSA

Cephalexin does not provide coverage against methicillin-resistant Staphylococcus aureus (MRSA). First-generation cephalosporins like cephalexin are ineffective against MRSA due to the presence of the mecA gene, which encodes for altered penicillin-binding proteins with significantly lower affinity for beta-lactams 1.

Mechanism of Resistance

• MRSA strains possess the mecA gene, which encodes a penicillin-binding protein (PBP2a) with significantly lower affinity for beta-lactams, including cephalexin 1
• The FDA drug label for cephalexin explicitly states: "Note—Methicillin-resistant staphylococci are resistant to cephalosporins, including cephalexin" 2
• First-generation cephalosporins like cephalexin are only effective against methicillin-susceptible S. aureus (MSSA) 3

Clinical Guidelines for MRSA Treatment

Recommended Oral Options for MRSA Infections:

• Linezolid 4
• Trimethoprim-sulfamethoxazole (TMP-SMX) 4
• Clindamycin (if the strain is susceptible) 4
• Doxycycline or minocycline 4

Recommended Intravenous Options for Severe MRSA Infections:

• Vancomycin (first-line therapy) 4
• Daptomycin 4
• Linezolid 4
• Ceftaroline (a fifth-generation cephalosporin with MRSA activity, unlike first-generation cephalosporins) 4

Evidence from Clinical Studies

• In a randomized, double-blind trial of patients with skin abscesses (87.8% of which were MRSA), cephalexin showed no benefit over placebo after incision and drainage, with cure rates of 84.1% for cephalexin versus 90.5% for placebo 5
• In another study comparing cefdinir to cephalexin for skin infections, both antibiotics showed similar cure rates for MRSA infections (92% vs. 90%), but this was likely due to adequate surgical drainage rather than antibiotic efficacy, as cephalosporins "do not have accepted, clinically relevant in vitro activity against MRSA" 6

Treatment Algorithm for Suspected Staphylococcal Infections

1. For mild infections with no risk factors for MRSA:

   • Cephalexin or other beta-lactams are appropriate empiric choices 4

2. For mild infections with MRSA risk factors (previous MRSA infection, recent hospitalization, recent antibiotic use):

   • Use TMP-SMX, clindamycin, doxycycline, or linezolid 4

3. For moderate to severe infections with MRSA risk factors:

   • Consider vancomycin, linezolid, or daptomycin 4

4. When culture results become available:

   • If MSSA: Continue or switch to beta-lactam (cephalexin is appropriate) 4, 3
   • If MRSA: Switch to an appropriate anti-MRSA agent 4, 1

Important Clinical Considerations

• Empiric coverage with cephalexin is only appropriate in settings with low MRSA prevalence or when MRSA has been ruled out 4
• Surgical drainage remains the primary treatment for purulent skin infections, regardless of antibiotic choice 5, 6
• The IWGDF/IDSA guidelines specifically recommend alternative agents (linezolid, TMP-SMX, clindamycin, doxycycline) for patients with high risk for MRSA, not cephalexin 4

Common Pitfalls

• Assuming all Staphylococcus aureus infections can be treated with cephalexin without obtaining cultures 4, 1
• Continuing cephalexin therapy after MRSA is identified in cultures 1, 3
• Failing to consider local resistance patterns when selecting empiric therapy 4
• Relying solely on antibiotics without adequate surgical drainage for purulent infections 5, 6