When to use amoxicillin-clavulanate (amoxyclav) and when to use cephalexin (cefalexine) in skin infections?

When to Use Amoxicillin-Clavulanate vs Cephalexin in Skin Infections

For most uncomplicated skin infections caused by Staphylococcus aureus and Streptococcus pyogenes, cephalexin is the preferred first-line agent, while amoxicillin-clavulanate should be reserved for infections requiring anaerobic coverage, particularly animal or human bites. 1, 2

Use Cephalexin for:

Uncomplicated Skin and Soft Tissue Infections

• Cephalexin is a WHO-designated first-choice antibiotic for mild, uncomplicated skin and soft tissue infections including impetigo, cellulitis, and simple abscesses when MRSA is not suspected 2
• The WHO Expert Committee elevated cephalexin from second-choice to first-choice status in 2021, placing it alongside amoxicillin-clavulanate as a preferred agent 2
• Standard adult dosing is 500 mg four times daily (or 250 mg four times daily for impetigo) 1

Non-Purulent Infections

• Cephalexin is specifically recommended by IDSA for non-purulent infections such as cellulitis where streptococcal coverage is paramount 2
• Clinical cure rates of 90% or higher are consistently achieved for streptococcal and staphylococcal skin infections 3

Purulent Infections (When MRSA Unlikely)

• Cephalexin is appropriate for purulent infections like furuncles and carbuncles only when local MRSA prevalence is low and the patient lacks MRSA risk factors 2
• If MRSA is suspected, switch to trimethoprim-sulfamethoxazole, doxycycline, or clindamycin instead 1, 2

Practical Advantages

• Cephalexin offers more convenient dosing and better suspension availability for pediatric patients compared to alternatives like dicloxacillin 1, 2
• A 5-day course is as effective as 10 days for uncomplicated infections showing clinical improvement 2

Use Amoxicillin-Clavulanate for:

Animal or Human Bites

• Amoxicillin-clavulanate is the mandatory first-line choice for all animal and human bites due to required anaerobic coverage, particularly against Pasteurella multocida in cat/dog bites 1, 2
• Standard dosing is 875/125 mg twice daily for adults 1
• Cephalexin, dicloxacillin, erythromycin, and clindamycin have poor activity against P. multocida and should never be used 1

Infections Requiring Anaerobic Coverage

• Amoxicillin-clavulanate is appropriate for surgical site infections involving the intestinal tract, genitourinary tract, axilla, or perineum where anaerobic bacteria are likely 2
• Use for infections associated with oral flora contamination or fecal contamination 1

Alternative for Standard Skin Infections

• Amoxicillin-clavulanate can be used as an alternative to cephalexin for impetigo and uncomplicated cellulitis, though it offers no advantage and has broader spectrum 1
• Consider when cephalexin is unavailable or not tolerated 1

Critical Situations Where NEITHER Should Be Used:

MRSA Infections

• Both cephalexin and amoxicillin-clavulanate lack activity against MRSA and must not be used when methicillin-resistant S. aureus is suspected or confirmed 1, 2
• Switch to vancomycin (IV), linezolid, daptomycin, ceftaroline, or oral agents like trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 1, 2

Necrotizing Infections

• Necrotizing fasciitis and gas gangrene require combination therapy with clindamycin plus piperacillin-tazobactam or ceftriaxone plus metronidazole 1, 2
• Penicillin plus clindamycin is recommended for group A streptococcal and clostridial necrotizing infections 1

Moderate-to-Severe Diabetic Foot Infections

• These require broader spectrum coverage than either agent provides; cephalexin is inadequate 2

Common Pitfalls to Avoid:

• Do not use cephalexin in areas with high MRSA prevalence (>10-15% of community S. aureus isolates) without considering anti-MRSA coverage 1, 2
• Do not assume all purulent infections are MRSA; beta-lactams like cephalexin were successful in 96% of cellulitis cases, suggesting MRSA cellulitis is uncommon 2
• Do not use amoxicillin-clavulanate routinely when cephalexin would suffice, as this promotes unnecessary broad-spectrum antibiotic use 1, 2
• For penicillin-allergic patients with immediate hypersensitivity reactions, neither agent is appropriate; use clindamycin, doxycycline, or a fluoroquinolone instead 1