Treatment of Bacterial Skin Infections
First-Line Treatment for Uncomplicated Cellulitis
For typical nonpurulent cellulitis in adults, beta-lactam monotherapy is the standard of care and achieves a 96% success rate, making MRSA coverage unnecessary in most cases. 1
Recommended Oral Beta-Lactam Options:
- Cephalexin 500 mg orally every 6 hours (four times daily) 1
- Dicloxacillin 250-500 mg every 6 hours 1
- Amoxicillin (dose equivalent to above agents) 1
- Penicillin V 250-500 mg four times daily 1
Treatment duration is exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 This represents a major shift from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 1
For Hospitalized Patients Requiring IV Therapy:
- Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1
- Alternatives include nafcillin or oxacillin 2 g IV every 6 hours 1
Treatment of Impetigo
For minor skin infections like impetigo, mupirocin 2% topical ointment is effective and should be the first-line treatment. 2
Systemic Options When Topical Therapy Fails:
- Cephalexin 250 mg four times daily in adults 1
- Cephalexin 25 mg/kg/day in four divided doses for children 1
- Dicloxacillin or erythromycin are alternatives 3
When to Add MRSA Coverage
MRSA coverage should be added ONLY when specific risk factors are present—not reflexively based on hospitalization or severity alone. 1
Specific MRSA Risk Factors Requiring Coverage:
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 2
- Evidence of MRSA infection elsewhere or documented nasal MRSA colonization 1
- Systemic inflammatory response syndrome (SIRS) 1
- Failure to respond to beta-lactam therapy within 48 hours 2
Oral MRSA-Active Regimens:
- Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, but use only if local clindamycin resistance is <10% 2
- Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily PLUS a beta-lactam (e.g., amoxicillin or cephalexin) 2
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam 2
- Linezolid 600 mg orally twice daily (expensive, reserve for complicated cases) 2
Critical caveat: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
Treatment of Complicated/Severe Cellulitis
For hospitalized patients with complicated skin and soft tissue infections (deeper infections, major abscesses, infected ulcers/burns), empirical MRSA therapy should be initiated pending culture data. 2
IV MRSA-Active Options (All A-I Evidence):
- Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line) 2
- Linezolid 600 mg IV twice daily 2, 4
- Daptomycin 4 mg/kg IV once daily 2
- Telavancin 10 mg/kg IV once daily 2
- Clindamycin 600 mg IV three times daily (only if local resistance <10%) 2
Treatment duration for complicated infections is 7-14 days, individualized based on clinical response. 2
For Severe Cellulitis with Systemic Toxicity or Suspected Necrotizing Fasciitis:
Mandatory broad-spectrum combination therapy is required immediately: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
- Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
- Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
Duration for severe infections: 7-10 days minimum, with reassessment at 5 days. 1
Special Populations and Situations
Pediatric Considerations:
- Mupirocin 2% topical ointment for minor infections like impetigo 2
- Never use tetracyclines in children <8 years of age 2
- For hospitalized children with complicated cellulitis: vancomycin 15 mg/kg IV every 6 hours 2
- Alternative for stable children without bacteremia: clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if local resistance <10%) 2
Penicillin/Cephalosporin Allergy:
- Clindamycin 300-450 mg orally every 6 hours is the optimal choice, providing single-agent coverage for both streptococci and MRSA 1
- For severe allergy: Vancomycin 15-20 mg/kg IV every 8-12 hours or linezolid 600 mg IV twice daily 1
Diabetic Foot Infections:
These require broader coverage and longer duration due to polymicrobial nature: 1
- Mild infections: amoxicillin-clavulanate, levofloxacin, or clindamycin 1
- Moderate infections: amoxicillin-clavulanate, levofloxacin, ceftriaxone, or ampicillin-sulbactam 1
- Severe infections: piperacillin-tazobactam, imipenem-cilastatin, or vancomycin plus ceftazidime ± metronidazole 1
Essential Adjunctive Measures
These non-antibiotic interventions are critical and often neglected: 1
- Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1
- Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat to eradicate colonization 1
- Address underlying venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves 1
- Incision and drainage is the primary treatment for abscesses—antibiotics play only a subsidiary role 2
Critical Pitfalls to Avoid
- Do not reflexively add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases resistance 1
- Do not extend treatment to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication 1
- Do not use doxycycline or TMP-SMX as monotherapy for cellulitis—they lack reliable streptococcal coverage 1
- Do not delay surgical consultation if necrotizing infection is suspected (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues) 1
- Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection 1
Recurrent Cellulitis Prevention
For patients with 3-4 episodes per year despite optimal management of risk factors: 1