What is the recommended treatment for cellulitis?

Treatment of Cellulitis

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage is unnecessary in most cases. 1

Recommended Oral Agents for Uncomplicated Cellulitis

• Penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin are all appropriate first-line options for typical nonpurulent cellulitis 1, 2
• These agents target β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, which account for the majority of identified pathogens in cellulitis 3, 4
• Cephalexin is a particularly practical choice for outpatient management due to its excellent streptococcal coverage and tolerability 1

Treatment Duration

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

• This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases 1
• Reassess patients at 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1

When to Add MRSA Coverage

MRSA coverage should be added ONLY when specific risk factors are present—not reflexively. 1, 2

Specific Indications for MRSA-Active Therapy

Add MRSA coverage when cellulitis is associated with:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Known MRSA colonization or evidence of MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) 1

MRSA-Active Regimens

When MRSA coverage is needed, use one of these options:

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

Critical caveat: Never use doxycycline or SMX-TMP as monotherapy for typical cellulitis, as they lack reliable activity against β-hemolytic streptococci 1

Inpatient Management and IV Antibiotics

When to Hospitalize

Admit patients with any of the following:

• Systemic toxicity (fever, hypotension, tachycardia, altered mental status) 1, 2
• 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
• Failure of outpatient treatment 2

IV Antibiotic Selection

For hospitalized patients with complicated cellulitis requiring MRSA coverage:

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
• Alternative agents with equivalent efficacy: linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or clindamycin 600 mg IV three times daily (if local MRSA resistance <10%) 1

For uncomplicated cellulitis requiring hospitalization but without MRSA risk factors:

• IV cefazolin or oxacillin remains appropriate, as beta-lactam monotherapy succeeds in 96% of cases even in the inpatient setting 1

Severe Infections Requiring Broad-Spectrum Coverage

For suspected necrotizing fasciitis or severe systemic toxicity:

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours 1
• Alternative combinations: vancomycin plus a carbapenem, or vancomycin plus ceftriaxone and metronidazole 1
• Obtain emergent surgical consultation for diagnostic and therapeutic debridement 1
• Duration: 7-14 days for necrotizing infections or those requiring surgical debridement 1

Transition to Oral Therapy

• Switch to oral antibiotics (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 1
• For continued MRSA coverage orally, use clindamycin alone or combination therapy with doxycycline or SMX-TMP plus a beta-lactam 1

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2

Additional supportive measures:

• Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema 1, 2
• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1, 2

Common Pitfalls to Avoid

Do not reflexively add MRSA coverage simply because the patient is hospitalized or because community MRSA rates are high—MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings. 1, 4

Distinguish cellulitis from purulent collections (abscesses, furuncles):

• Purulent collections require incision and drainage as primary treatment, with antibiotics playing a subsidiary role 1
• Use ultrasound if there is clinical uncertainty about the presence of an abscess 1

If cellulitis is spreading despite appropriate antibiotics (e.g., cloxacillin):

• Reassess for necrotizing fasciitis warning signs immediately 1
• Consider MRSA or resistant organisms 1
• Switch to vancomycin or linezolid if MRSA is suspected 1
• Do not continue ineffective antibiotics beyond 48 hours 1

Prevention of Recurrence

For patients with 3-4 episodes per year despite treatment of predisposing factors:

• Consider prophylactic antibiotics (oral penicillin, erythromycin, or intramuscular benzathine penicillin) 2, 5
• Address underlying conditions: edema, obesity, venous insufficiency, toe web abnormalities 1, 2