What is the treatment for cellulitis of the leg?

Treatment for Cellulitis of the Leg

Beta-lactam monotherapy for 5 days is the standard of care for typical uncomplicated leg cellulitis, as MRSA coverage is unnecessary in 96% of cases. 1

First-Line Antibiotic Selection

For typical nonpurulent leg cellulitis, use beta-lactam monotherapy with one of the following oral agents: 1

• Cephalexin (most commonly used)
• Dicloxacillin 250-500 mg every 6 hours
• Amoxicillin or amoxicillin-clavulanate
• Penicillin
• Clindamycin (covers both streptococci and MRSA if local resistance <10%)

The rationale is straightforward: typical leg cellulitis is caused by beta-hemolytic streptococci and methicillin-sensitive S. aureus, not MRSA, even in hospitals with high MRSA prevalence. 1, 2 Beta-lactam treatment succeeds in 96% of patients, confirming that reflexive MRSA coverage is overtreatment. 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Known MRSA colonization or prior MRSA infection
• Systemic inflammatory response syndrome (SIRS)
• Failure to respond to beta-lactam therapy after 48 hours

If MRSA coverage is needed, use combination therapy: 1

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

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci. 1

Adjunctive Measures (Mandatory, Not Optional)

Elevation of the affected leg hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1 This is not a suggestion—it's a required component of treatment.

Identify and treat predisposing factors: 1, 3

• Tinea pedis and toe web abnormalities (examine interdigital spaces)
• Venous insufficiency and chronic edema
• Venous eczema (provides bacterial entry points)
• Lymphedema
• Obesity

Addressing these factors reduces recurrence rates, which otherwise range from 8-20% annually. 3

Consideration of Systemic Corticosteroids

Prednisone 40 mg daily for 7 days could be considered in non-diabetic adults to reduce inflammation, though evidence is limited. 1, 3 This is a weak recommendation with moderate evidence, so use clinical judgment.

Hospitalization Criteria

Hospitalize if any of the following are present: 1, 3

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status
• Severe immunocompromise or neutropenia
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes)
• Hemodynamic instability
• Poor adherence anticipated

Inpatient IV Antibiotic Selection

For hospitalized patients with uncomplicated cellulitis requiring IV therapy, use cefazolin 1-2 g IV every 8 hours or oxacillin. 1 Beta-lactam monotherapy remains appropriate even in the inpatient setting if the cellulitis is nonpurulent and lacks MRSA risk factors. 1

For complicated cellulitis requiring MRSA coverage, use vancomycin 15-20 mg/kg IV every 8-12 hours as first-line. 1 Alternatives include linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or clindamycin 600 mg IV three times daily (if local resistance <10%). 1

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis, use broad-spectrum combination therapy: 1

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours, OR
• Vancomycin PLUS a carbapenem, OR
• Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours

Treat severe infections for 7-14 days depending on clinical response. 1

Transition to Oral Therapy

Transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 1 Use cephalexin, dicloxacillin, or clindamycin for continued coverage. 1

Management of Treatment Failure

If cellulitis spreads despite appropriate antibiotics after 48 hours, reassess for: 1

• Necrotizing fasciitis (obtain emergent surgical consultation)
• MRSA infection (switch to vancomycin or linezolid)
• Misdiagnosis (consider alternative diagnoses like deep vein thrombosis, venous stasis dermatitis)
• Deeper infection (abscess requiring drainage)

Never continue ineffective antibiotics beyond 48 hours. 1 Progression despite appropriate therapy indicates either resistant organisms or a different/deeper infection than initially recognized.

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite controlling predisposing factors, consider prophylactic penicillin or erythromycin twice daily for 4-52 weeks. 3 Alternatively, intramuscular benzathine penicillin G monthly can be used, though it benefits only patients without predisposing factors. 4

Special Consideration: Venous Stasis Cellulitis

For cellulitis associated with venous stasis, beta-lactam antibiotics for 5 days MUST be combined with aggressive treatment of venous eczema, edema, and interdigital abnormalities. 3 Elevation is particularly critical in this population. 3 Venous insufficiency and lymphedema significantly increase recurrence frequency. 3