What is the recommended treatment for outpatient lower extremity cellulitis?

Outpatient Treatment of Lower Extremity Cellulitis

For typical nonpurulent lower extremity cellulitis, treat with beta-lactam monotherapy (cephalexin 500mg twice daily, dicloxacillin 250-500mg every 6 hours, or amoxicillin) for 5 days, extending only if symptoms have not improved. 1

First-Line Antibiotic Selection

Beta-lactam monotherapy is the standard of care for uncomplicated lower extremity cellulitis, with a 96% success rate. 1 This high success rate confirms that MRSA coverage is unnecessary in typical cases, even in settings with high MRSA prevalence. 1

Recommended oral beta-lactam options include: 1

• Cephalexin 500mg orally twice daily
• Dicloxacillin 250-500mg orally every 6 hours
• Amoxicillin (standard dosing)
• Amoxicillin-clavulanate 875/125mg twice daily
• Cefuroxime 500mg orally twice daily 1

The pathogen in nonpurulent cellulitis, when isolated (which occurs in <20% of cases), is predominantly β-hemolytic streptococci or methicillin-sensitive S. aureus. 1 MRSA is an uncommon cause of typical cellulitis. 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs. 1 Extend treatment beyond 5 days only if the infection has not improved within this timeframe. 1 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

Reassess the patient in 24-48 hours to verify clinical response, as treatment failure can occur. 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 evidence of MRSA infection elsewhere
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min 1

If MRSA coverage is needed, use: 1

• Clindamycin 300-450mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., TMP-SMX plus cephalexin) 1
• Doxycycline 100mg orally twice daily PLUS a beta-lactam 1

Note that clindamycin should only be used if local MRSA clindamycin resistance rates are <10%. 1

Critical Pitfalls to Avoid

Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis. 1 These agents have unreliable activity against beta-hemolytic streptococci, which are the primary pathogens. 1 They must always be combined with a beta-lactam when treating nonpurulent cellulitis. 1

Do not reflexively add MRSA coverage for typical nonpurulent cellulitis. 1 Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases and represents overtreatment. 1 One study from Hawaii with high MRSA prevalence showed TMP-SMX had higher success rates than cephalexin (91% vs 74%), 2 but this contradicts the IDSA guideline evidence showing 96% success with beta-lactams alone. 1 The guideline evidence takes precedence, and MRSA coverage should be reserved for cases with specific risk factors.

Adjunctive Measures

Elevate the affected extremity to promote gravitational drainage of edema and hasten improvement. 1

Examine and treat predisposing conditions: 1

• Inspect interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration
• Treat toe web abnormalities to eradicate colonization and reduce recurrence risk
• Address venous insufficiency, lymphedema, chronic edema, and eczema

When to Hospitalize

Hospitalize if any of the following are present: 1

• Systemic inflammatory response syndrome (SIRS)
• Hypotension or hemodynamic instability
• Altered mental status or confusion
• Severe immunocompromise or neutropenia
• Concern for necrotizing fasciitis or deeper infection

Warning signs of necrotizing fasciitis include: 1

• Severe pain out of proportion to examination findings
• Skin anesthesia
• Rapid progression despite antibiotics
• Gas in tissue
• Bullous changes
• Systemic toxicity

If necrotizing infection is suspected, initiate broad-spectrum combination therapy (vancomycin or linezolid PLUS piperacillin-tazobactam) and obtain emergent surgical consultation. 1

Special Populations and Allergy Considerations

For penicillin-allergic patients: 1

• Clindamycin 300-450mg orally every 6 hours (covers both streptococci and MRSA)
• Levofloxacin 500mg daily (reserve for beta-lactam allergies; 5-day course is as effective as 10 days) 1

For patients allergic to both penicillin and sulfonamides: 1

• Clindamycin 300-450mg orally every 6 hours is the optimal choice

For bite-associated cellulitis (animal or human): 1

• Amoxicillin-clavulanate 875/125mg twice daily provides single-agent coverage for polymicrobial oral flora

Algorithm for Decision-Making

1. Assess for purulent drainage, abscess, or fluctuance → If present, incision and drainage is primary treatment; antibiotics are subsidiary 1

2. Evaluate for MRSA risk factors (penetrating trauma, injection drug use, purulent drainage, known MRSA colonization, SIRS) 1

   • If NO risk factors: Beta-lactam monotherapy (cephalexin, dicloxacillin, or amoxicillin) for 5 days 1
   • If risk factors present: Clindamycin monotherapy OR TMP-SMX/doxycycline plus beta-lactam for 5 days 1

3. Assess for systemic toxicity or necrotizing infection → If present, hospitalize for IV broad-spectrum combination therapy 1

4. Reassess at 24-48 hours → If not improving, consider resistant organisms, misdiagnosis (venous insufficiency, eczema, DVT, gout), or deeper infection 1

5. Address predisposing factors (tinea pedis, venous insufficiency, lymphedema) to prevent recurrence 1