Cephalexin for Staphylococcus Aureus Infections
Cephalexin is an excellent choice for confirmed methicillin-susceptible Staphylococcus aureus (MSSA) infections, but it has absolutely zero activity against MRSA and must never be used when MRSA is suspected or confirmed. 1
Critical Decision Point: MSSA vs MRSA
The appropriateness of cephalexin hinges entirely on methicillin susceptibility:
For MSSA Infections (Confirmed by Culture)
- Cephalexin 500 mg four times daily orally for 7 days is the recommended oral agent of choice for adults with uncomplicated MSSA skin and soft tissue infections 2, 1
- Pediatric dosing: 25-50 mg/kg/day divided into 3-4 doses 2, 1
- Cephalexin demonstrates cure rates of 90% or higher for streptococcal and staphylococcal skin infections 3
- The FDA specifically approves cephalexin for skin and skin structure infections caused by Staphylococcus aureus 4
For MRSA Infections (Confirmed or Suspected)
- Switch immediately to clindamycin (300-450 mg three times daily), doxycycline (100 mg twice daily), or trimethoprim-sulfamethoxazole—never use cephalexin 1, 2
- Cephalexin has zero in vitro activity against MRSA despite paradoxical clinical response rates reported in some studies, which likely reflect spontaneous drainage or incision and drainage procedures rather than antibiotic efficacy 5, 1
Empiric Therapy Considerations
For nonpurulent cellulitis (no drainage, no abscess), empiric beta-lactam therapy including cephalexin is appropriate as beta-hemolytic streptococci are the primary pathogens 2
For purulent cellulitis or abscesses, empiric coverage for community-acquired MRSA is mandatory—do not use cephalexin empirically in this setting 2
When to Modify Therapy
- If a patient with nonpurulent cellulitis fails to respond to cephalexin within 48-72 hours, switch to MRSA-active therapy (clindamycin, TMP-SMX, or doxycycline) 2
- Always obtain cultures from purulent infections to guide definitive therapy 2
Comparative Efficacy
- Cephalexin is comparable to other first-generation cephalosporins (cefazolin, cefadroxil), penicillinase-resistant penicillins (dicloxacillin), and clindamycin for MSSA infections 2, 6, 7
- For serious MSSA infections requiring parenteral therapy, nafcillin, oxacillin, or cefazolin are preferred over oral cephalexin 2
Common Pitfalls to Avoid
Never assume susceptibility without culture confirmation in the current era of widespread MRSA 1
Do not use cephalexin for hospitalized patients with complicated skin and soft tissue infections—these require parenteral therapy with vancomycin, linezolid, or daptomycin pending culture results 2
Avoid cephalexin in patients with immediate penicillin hypersensitivity reactions (urticaria, angioedema, bronchospasm, anaphylaxis) due to cross-reactivity risk 6