Treatment of Skin Infections
For uncomplicated skin and soft tissue infections, initiate treatment with a penicillinase-resistant semisynthetic penicillin (dicloxacillin 500 mg four times daily) or a first-generation cephalosporin (cephalexin 500 mg four times daily) to cover both Staphylococcus aureus and Streptococcus pyogenes. 1
Initial Antibiotic Selection Based on Infection Type
For Simple Cellulitis or Erysipelas
- Erysipelas (streptococcal): Penicillin is the treatment of choice, given either parenterally or orally depending on clinical severity 1
- Cellulitis (mixed staphylococcal/streptococcal): A penicillinase-resistant semisynthetic penicillin or first-generation cephalosporin should be selected 1
- These recommendations carry Grade A-I evidence (good evidence from randomized controlled trials) 1
For Impetigo (Limited Lesions)
- Topical therapy: Mupirocin ointment applied three times daily for patients with limited lesions 1
- Oral therapy if needed:
For MRSA Skin Infections
If methicillin-resistant S. aureus is suspected or confirmed:
- Parenteral: Vancomycin 30 mg/kg/day in 2 divided doses IV (adults) or 40 mg/kg/day in 4 divided doses IV (children) 1
- Oral alternatives:
Management of Penicillin Allergy
For Non-Severe Penicillin Allergy History
- First-generation cephalosporins are safe: Cefazolin 1 g every 8 hours IV or cephalexin 500 mg four times daily orally can be used, except in patients with immediate hypersensitivity reactions (urticaria, angioedema, bronchospasm, anaphylaxis) 1
- Cross-reactivity between penicillins and first-generation cephalosporins is higher, but second- and third-generation cephalosporins (cefuroxime, cefdinir, cefpodoxime, ceftriaxone) have negligible cross-reactivity due to different chemical structures 1
- The historically cited 10% cross-reactivity rate is an overestimate; actual rates are approximately 0.1% when severe reactions are excluded 1
For Severe Penicillin Allergy or Immediate Hypersensitivity
- Clindamycin: 600 mg every 8 hours IV or 300-450 mg three times daily orally 1
- Caveat: Potential for cross-resistance with erythromycin-resistant strains and inducible resistance in MRSA 1
- Doxycycline/Minocycline: 100 mg twice daily orally (not recommended for children <8 years) 1
- TMP-SMX: 1-2 double-strength tablets twice daily orally 1
Special Circumstances
Animal or Human Bites
- Non-penicillin allergic: Amoxicillin-clavulanate 875/125 mg twice daily orally or ampicillin-sulbactam 1.5-3.0 g every 6 hours IV 1
- Penicillin allergic with severe reactions: Doxycycline, TMP-SMX, or a fluoroquinolone plus clindamycin 1
- Rationale: Coverage needed for Pasteurella multocida (in animal bites) and Eikenella corrodens (in human bites), plus anaerobes 1
Necrotizing Infections
- Group A streptococcal/clostridial: Parenteral clindamycin plus penicillin (Grade A-II recommendation) 1
- Polymicrobial: Broad-spectrum coverage against aerobic gram-positive, gram-negative bacteria, and anaerobes 1
- Critical: Prompt surgical intervention is mandatory 1
Key Clinical Pitfalls
Common Errors to Avoid
- Do not use dicloxacillin, cephalexin, erythromycin, or clindamycin for animal bites due to poor activity against Pasteurella multocida 1
- Avoid oral M penicillins due to poor pharmacokinetic-pharmacodynamic parameters 2
- Erythromycin resistance: 18.7% of S. aureus strains show resistance; verify susceptibility before use 1, 3
- Penicillin/ampicillin resistance: 89.5% of S. aureus strains are resistant; these should not be used as monotherapy 3
When to Obtain Cultures
- Aspiration of cellulitis is unhelpful in 75-80% of cases, and blood cultures are positive in <5% 1
- Obtain cultures when:
Duration and Route
- Oral therapy: Typically 7 days depending on clinical response 1
- IV to oral switch: Maintain IV route until regression of general signs, then switch to oral therapy with the same drug 2
- Clinical improvement expected: Within 48-72 hours; if not improved, consider resistant organisms or alternative diagnosis 1