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 48-72 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 the following:

• 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 therapy 2

IV Antibiotic Selection for Hospitalized Patients

For complicated cellulitis requiring hospitalization, vancomycin 15-20 mg/kg IV every 8-12 hours is the first-line agent (A-I evidence). 1

Alternative IV agents with equivalent efficacy include:

• Linezolid 600 mg IV twice daily (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV three times daily (A-III evidence, only if local MRSA resistance <10%) 1

For severe infections with systemic toxicity or suspected necrotizing fasciitis, use broad-spectrum combination therapy: vancomycin or linezolid PLUS piperacillin-tazobactam, a carbapenem, or ceftriaxone plus metronidazole 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
• Appropriate oral options include cephalexin, dicloxacillin, or clindamycin 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

Critical Pitfalls to Avoid

Do Not Reflexively Add MRSA Coverage

• MRSA is an uncommon cause of typical cellulitis, even in hospitals with high MRSA prevalence 1, 2
• Beta-lactam monotherapy succeeds in 96% of cases without MRSA risk factors 1
• Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases 1

Distinguish Cellulitis from Purulent Collections

• Abscesses and furuncles require incision and drainage as primary treatment, not antibiotics alone 1
• Use ultrasound if clinical uncertainty exists about the presence of a purulent collection 1

Recognize Necrotizing Fasciitis Early

Warning signs requiring emergent surgical consultation:

• Severe pain out of proportion to examination 1
• Skin anesthesia, rapid progression, gas in tissue, bullous changes 1
• Do not delay surgical consultation if any signs of necrotizing infection are present 1

Prevention of Recurrence

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

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