What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy with oral agents such as cephalexin, dicloxacillin, or amoxicillin for 5 days is the standard of care, achieving success in 96% of patients without requiring MRSA coverage. 1

First-Line Antibiotic Selection

For outpatient management of uncomplicated cellulitis:

• Cephalexin 500 mg orally four times daily is a preferred first-line agent providing excellent streptococcal and methicillin-sensitive S. aureus coverage 1
• Dicloxacillin 250-500 mg orally every 6 hours is equally effective, taken on an empty stomach at least 1 hour before or 2 hours after meals with at least 4 ounces of water 1, 2
• Amoxicillin or penicillin V 250-500 mg orally four times daily are alternative beta-lactam options 1
• Treatment duration is exactly 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe 1, 3

Critical point: MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases 1, 3

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or evidence of MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) 1

For cellulitis requiring MRSA coverage:

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, avoiding the need for combination therapy 1, 4
• Use clindamycin only if local MRSA resistance rates are <10% 1
• Alternative: Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline alone is inadequate due to unreliable streptococcal coverage) 1
• Alternative: Trimethoprim-sulfamethoxazole PLUS a beta-lactam 1

Inpatient Management

Hospitalize patients with: 1

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1

For hospitalized patients with uncomplicated cellulitis without MRSA risk factors:

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1
• Oxacillin 2 g IV every 6 hours is an alternative 1
• Transition to oral therapy (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after minimum 4 days of IV treatment 1

For hospitalized patients requiring MRSA coverage:

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
• Linezolid 600 mg IV twice daily is equally effective (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily is an alternative (A-I evidence) 1
• Clindamycin 600 mg IV every 8 hours if local resistance is low (A-III evidence) 1

Severe Cellulitis with Systemic Toxicity

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: 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: 7-14 days guided by clinical response 1
• Obtain emergent surgical consultation if necrotizing fasciitis is suspected 1

Special Situations

For bite-associated cellulitis (human or animal):

• Amoxicillin-clavulanate (Augmentin) 875/125 mg orally twice daily provides single-agent coverage for polymicrobial oral flora 1

For penicillin-allergic patients:

• Clindamycin 300-450 mg orally every 6 hours covers both streptococci and MRSA 1, 4
• Levofloxacin 500 mg daily is an alternative for patients with beta-lactam allergies 1

For cephalosporin-allergic patients:

• Penicillin V 250-500 mg orally four times daily provides excellent streptococcal coverage 1
• Clindamycin is an alternative 1
• Carbapenems can be safely used in cephalosporin-allergic patients 1

Essential Adjunctive Measures

These 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, 5
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat to eradicate colonization and reduce recurrence 1
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, eczema, obesity 1, 5
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 6

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors: 1

• Prophylactic penicillin V 250 mg orally twice daily 1
• Alternative: Erythromycin 250 mg orally twice daily 1
• Annual recurrence rates are 8-20% in patients with previous leg cellulitis 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment 1, 7
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection 1
• Do not delay surgical consultation if any signs of necrotizing infection are present, as these progress rapidly 1
• Reassess patients in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1