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 and should be used in 96% of cases, as MRSA coverage is unnecessary for nonpurulent cellulitis without specific risk factors. 1

Recommended Oral Agents for Outpatient Treatment

• Cephalexin 500 mg four times daily is a preferred first-line option for typical cellulitis 1
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and methicillin-sensitive S. aureus coverage 1
• Amoxicillin is appropriate for typical nonpurulent cellulitis 1
• Penicillin V 250-500 mg four times daily is an alternative option 1
• Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily should be reserved specifically for bite-associated cellulitis (human or animal) 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 This represents a major shift from traditional 7-14 day courses and is supported by high-quality randomized controlled trial evidence 1. The 5-day duration applies whether using oral or IV antibiotics 1.

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical nonpurulent cellulitis. 1 MRSA is an uncommon cause of typical cellulitis even in hospitals with high MRSA prevalence 1.

Specific Indications for MRSA-Active Antibiotics

Add MRSA coverage ONLY when these risk factors are present:

• 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) with fever >38°C, tachycardia >90 bpm, or tachypnea >24 rpm 1

MRSA-Active Regimens When Indicated

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

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

Inpatient IV Antibiotic Selection

Indications for Hospitalization

Hospitalize if ANY of the following are present:

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing fasciitis or deeper infection 1

Standard IV Therapy for Uncomplicated Cellulitis Requiring Hospitalization

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for hospitalized patients without MRSA risk factors 1
• Oxacillin 2 g IV every 6 hours or nafcillin 2 g IV every 6 hours are alternatives 1

IV Therapy for Complicated Cellulitis with MRSA Risk Factors

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line with A-I level 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 MRSA resistance <10% (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

Recommended IV Combination Regimens

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

For documented group A streptococcal necrotizing fasciitis specifically: Use penicillin plus clindamycin 1

Treatment duration for severe infections is 7-14 days, guided by clinical response 1.

Essential Adjunctive Measures

These are often neglected but critical for treatment success:

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1
• Examine interdigital toe spaces for tinea pedis (fissuring, scaling, maceration) and treat to eradicate colonization and reduce recurrence 1
• Treat predisposing conditions: venous insufficiency, lymphedema, chronic edema, eczema, and obesity 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Special Populations and Situations

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours is the optimal choice, providing single-agent coverage for both streptococci and MRSA 1
• Levofloxacin 500 mg daily can be used but should be reserved for patients with beta-lactam allergies 1

Diabetic Foot Cellulitis

• Amoxicillin-clavulanate, ampicillin-sulbactam, or second/third-generation cephalosporins (cefuroxime, cefotaxime, ceftriaxone) for moderate infections 1

Pediatric Dosing

• Vancomycin 15 mg/kg IV every 6 hours for hospitalized children with complicated cellulitis 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours if stable, no bacteremia, and local resistance <10% 1
• Linezolid: 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years 1

Transition to Oral Therapy

Patients can transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 1 Use cephalexin, dicloxacillin, or clindamycin for continued coverage 1.

Prevention of Recurrent Cellulitis

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

Prophylactic Antibiotics

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

• Penicillin V 250 mg orally twice daily 1
• Erythromycin 250 mg twice daily 1
• Intramuscular benzathine penicillin 2

Critical Warning Signs Requiring Immediate Reassessment

If cellulitis spreads despite appropriate antibiotics within 24-48 hours, immediately evaluate for: 1

• Necrotizing fasciitis: severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, bullous changes 1
• MRSA involvement if not initially covered 1
• Misdiagnosis: consider pseudocellulitis (venous stasis dermatitis, contact dermatitis, DVT) 3, 4

Obtain emergent surgical consultation if necrotizing infection is suspected, as these progress rapidly and require debridement. 1