What is the recommended treatment for cellulitis?

Cellulitis Treatment

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

• Cephalexin 500 mg four times daily for 5 days is highly effective for typical nonpurulent cellulitis 1
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and methicillin-sensitive S. aureus coverage 1
• Amoxicillin or penicillin V 250-500 mg four times daily are appropriate alternatives 1, 2
• Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily is specifically indicated for bite-associated cellulitis 1

Intravenous Options for Hospitalized Patients

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 1
• Nafcillin 2 g IV every 6 hours or oxacillin 2 g IV every 6 hours are alternatives 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2 This represents a major shift from traditional 7-14 day courses and is supported by high-quality randomized controlled trial evidence 1

When to Add MRSA Coverage

Specific Risk Factors Requiring MRSA-Active Antibiotics

MRSA coverage should be added only when the following specific risk factors are present 1, 2:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (SIRS) with fever >38°C, tachycardia >90 bpm, or tachypnea >24 rpm 1

MRSA-Active Regimens

When MRSA coverage is indicated 1:

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA (use only if local resistance <10%) 1
• Trimethoprim-sulfamethoxazole (Bactrim) PLUS a beta-lactam (e.g., cephalexin) for combination therapy 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam for combination therapy 1

Critical caveat: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1

Severe Cellulitis Requiring Hospitalization

Indications for Hospitalization 1, 2

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

IV Antibiotic Regimens for Severe Infection

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy includes: 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, 3
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1

Treatment duration for severe infections: 7-14 days guided by clinical response 1

MRSA-Active IV Monotherapy Options (for complicated cellulitis without necrotizing features) 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence)
• Linezolid 600 mg IV twice daily (A-I evidence) 3
• Daptomycin 4 mg/kg IV once daily (A-I evidence)
• Clindamycin 600 mg IV every 8 hours (only if local resistance <10%)

Essential Adjunctive Measures

Elevation of the affected extremity is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2

Additional measures 1, 2:

• Examine interdigital toe spaces for tinea pedis (fissuring, scaling, maceration) and treat to eradicate colonization and reduce recurrence risk
• Address venous insufficiency and lymphedema with compression stockings once acute infection resolves
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Pediatric Dosing

Oral Therapy 1

• Children <5 years: 10 mg/kg orally every 8 hours
• Children 5-11 years: 10 mg/kg orally every 12 hours
• Adolescents ≥12 years: Adult dosing (600 mg every 12 hours for linezolid; weight-based for beta-lactams)

IV Therapy for Hospitalized Children 1

• Vancomycin 15 mg/kg IV every 6 hours (first-line)
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if local resistance <10%)
• Linezolid: 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years 3

Never use doxycycline in children under 8 years of age due to tooth discoloration and bone growth effects 1

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because community-associated MRSA prevalence is high—beta-lactam monotherapy succeeds in 96% of typical cases 1, 4
• 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 and require debridement 1
• Do not use combination therapy (e.g., cephalexin plus trimethoprim-sulfamethoxazole) for pure cellulitis without abscess, ulcer, or purulent drainage—it provides no additional benefit 1

Prevention of Recurrent Cellulitis

Annual recurrence rates are 8-20% in patients with previous leg cellulitis 1

For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics: 1, 2

• Penicillin V 250 mg orally twice daily, or
• Erythromycin 250 mg orally twice daily

Special Populations

Penicillin/Cephalosporin Allergy 1

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA if local resistance <10%)
• Levofloxacin 500 mg daily (reserve for true beta-lactam allergies)

Diabetic Foot Infections 1

• Amoxicillin-clavulanate or ampicillin-sulbactam for moderate infections
• Consider broader coverage with cefuroxime, cefotaxime, or ceftriaxone