What is the initial treatment for localized cellulitis?

Treatment of Localized Cellulitis

First-Line Antibiotic Therapy

For typical uncomplicated cellulitis, beta-lactam monotherapy is the standard of care and is successful in 96% of patients. 1, 2

• Recommended oral agents include:

  • Cephalexin 500 mg four times daily 2, 3
  • Dicloxacillin 250 mg every 6 hours for moderate infections 1, 4
  • Amoxicillin 1, 2
  • Penicillin 1, 2
  • Clindamycin 300-450 mg three times daily 2, 5

• MRSA coverage is NOT needed for typical nonpurulent cellulitis, as MRSA is an uncommon cause even in high-prevalence settings. 1, 2

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 2

• Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 2
• Reassess at 48-72 hours to verify clinical response. 2, 5

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or known MRSA colonization 2, 3
• Failure to respond to beta-lactam therapy after 48 hours 2

MRSA-active options include: 1, 2

• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam 2
• Doxycycline 100 mg twice daily PLUS a beta-lactam 2
• Clindamycin monotherapy (covers both streptococci and MRSA) 2, 5

Critical caveat: Doxycycline and TMP-SMX lack reliable activity against beta-hemolytic streptococci and must never be used as monotherapy for typical cellulitis. 2

Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema and hasten improvement. 2, 3
• Treat predisposing conditions including tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, and obesity. 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited. 2, 3

Indications for Hospitalization

Hospitalize if any of the following are present: 2, 3

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1, 2
• Severe pain out of proportion to examination (concern for necrotizing fasciitis) 2
• Rapid progression despite appropriate antibiotics 2
• Severe immunocompromise or neutropenia 1
• Poor adherence to outpatient therapy 3

For hospitalized patients with uncomplicated cellulitis: 2

• IV cefazolin or oxacillin remains appropriate for nonpurulent cellulitis without MRSA risk factors 2
• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis requiring MRSA coverage 2
• Transition to oral therapy once clinical improvement is demonstrated, typically after minimum 4 days IV treatment 2

When Treatment Fails

If cellulitis spreads despite appropriate antibiotics after 48 hours: 2

1. Immediately assess for necrotizing fasciitis: severe pain out of proportion, skin anesthesia, bullous changes, gas in tissue, or systemic toxicity 2
2. Obtain emergent surgical consultation if necrotizing infection suspected 2
3. Switch to vancomycin or linezolid if MRSA suspected or systemic toxicity present 2
4. Consider misdiagnosis: venous stasis dermatitis, contact dermatitis, eczema, or lymphedema can mimic cellulitis 6

Never continue ineffective antibiotics beyond 48 hours as progression indicates resistant organisms or deeper infection. 2

Common Causes of Tender Red Bumps

Tender red bumps require differentiation from cellulitis: 1

• Furuncles (boils): localized purulent collections requiring incision and drainage, not antibiotics alone 1
• Abscesses: fluctuant collections requiring drainage as primary treatment 1
• Septic bursitis: purulent collection in bursa requiring drainage plus antibiotics 1

The distinction is clinically crucial: cellulitis requires antibiotics as primary treatment, while purulent collections require drainage with antibiotics having a subsidiary role. 1

Penicillin Allergy Alternatives

For patients with penicillin/amoxicillin allergies: 5

• Clindamycin 300-450 mg orally three times daily is the preferred alternative, providing coverage against both streptococci and staphylococci 5
• Doxycycline 100 mg twice daily (avoid in children under 8 years) 5
• TMP-SMX 1-2 double-strength tablets twice daily 5

Avoid cephalosporins in patients with immediate hypersensitivity reactions to penicillins due to potential cross-reactivity. 5