Recommended First-Generation Cephalosporin for Skin and Soft Tissue Infections
Cephalexin (cefalexin) is the recommended first-generation cephalosporin for skin and soft tissue infections, designated as a first-line agent by the WHO Essential Medicines List and IDSA guidelines. 1, 2
Primary Recommendation
The WHO Expert Committee elevated cephalexin from second-choice to first-choice status in 2021 specifically for skin and soft tissue infections. 1 This designation places it alongside amoxicillin-clavulanate and cloxacillin as preferred agents for mild infections. 1
Why Cephalexin Over Cefazolin
While both cephalexin (oral) and cefazolin (intravenous) are first-generation cephalosporins with similar antimicrobial coverage, cephalexin is preferred for outpatient management due to its oral bioavailability and convenient dosing schedule. 1, 2, 3
- Cephalexin dosing: 500 mg orally three times daily for adults, or every 12 hours for streptococcal pharyngitis and uncomplicated skin infections 1, 3
- Cefazolin dosing: 1 g intravenously every 8 hours, requiring hospitalization or home infusion 1
- Pediatric cephalexin: 25-50 mg/kg/day in divided doses 3
Spectrum of Activity and Clinical Indications
Cephalexin provides excellent coverage against staphylococci and streptococci, the primary pathogens in most skin and soft tissue infections. 1, 2
Specific IDSA-Approved Indications:
- Impetigo in pediatric and adult patients 2
- Purulent skin and soft tissue infections likely due to methicillin-susceptible Staphylococcus aureus 2
- Non-purulent skin and soft tissue infections (cellulitis, erysipelas) 2
- Incisional surgical site infections after trunk or extremity surgery (away from axilla/perineum) 1
Comparative Effectiveness:
Meta-analysis demonstrates no significant difference in treatment outcomes between penicillins and cephalosporins for cellulitis (RR 0.99; 95% CI 0.68-1.43). 1, 2 However, cephalexin showed superior cure rates compared to penicillin alone (RR 1.59; 95% CI 1.21-2.08) in impetigo. 1
Critical Coverage Gaps and When NOT to Use Cephalexin
MRSA Infections - Absolute Contraindication:
Do not use cephalexin if MRSA is suspected or confirmed. 2 Red flags include:
- Purulent drainage with abscess formation 2
- Penetrating trauma 2
- Concurrent MRSA infection at another site 2
- Known high local MRSA prevalence 2
For MRSA coverage, switch to: vancomycin, linezolid, daptomycin, clindamycin, doxycycline, or trimethoprim-sulfamethoxazole. 1, 2
Animal Bites - Poor Coverage:
Cephalexin has poor activity against Pasteurella multocida and should be avoided for animal bites. 1, 2 Use amoxicillin-clavulanate instead for dog and cat bites. 1, 2
Anaerobic Infections:
First-generation cephalosporins miss anaerobes. 1 For infections involving the axilla or perineum where anaerobes are likely, use ceftriaxone plus metronidazole or a beta-lactam/beta-lactamase inhibitor combination. 1
Human Bites:
Cephalexin misses Eikenella corrodens and gram-negative anaerobes common in human bites. 1 Use amoxicillin-clavulanate or ampicillin-sulbactam instead. 1
Dual Coverage Strategy for Uncertain MRSA Status
When streptococcal coverage is needed but MRSA cannot be excluded, combine cephalexin with either trimethoprim-sulfamethoxazole or doxycycline. 2 This provides:
Treatment Duration
Typical treatment duration is 5-14 days depending on clinical response. 2 For beta-hemolytic streptococcal infections, administer for at least 10 days. 3
Common Pitfall to Avoid
The most critical error is using cephalexin for purulent infections without considering MRSA. 2 In the current era of community-associated MRSA, any purulent skin infection with abscess formation should prompt consideration of anti-MRSA therapy rather than first-generation cephalosporins. 2