What is the recommended management for cellulitis?

Management 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

Oral Regimens for Outpatient Management

• Cephalexin 500 mg four times daily is a preferred first-line agent 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
• Amoxicillin-clavulanate 875/125 mg twice daily is specifically recommended for bite-associated cellulitis (human or animal) as it provides single-agent polymicrobial coverage 1

Intravenous Regimens 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 occurs; extend only if symptoms have not improved within this timeframe. 1 This represents a significant departure from traditional 7-14 day courses and is supported by high-quality randomized controlled trial evidence 1

When to Add MRSA Coverage

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

Risk Factors Requiring MRSA Coverage

• 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) 1
• Failure to respond to beta-lactam therapy after 48 hours 1

MRSA-Active Regimens

For oral therapy requiring MRSA coverage:

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

Critical caveat: Doxycycline or SMX-TMP should never be used as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1

For IV therapy requiring MRSA coverage:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1
• Linezolid 600 mg IV twice daily (A-I evidence) 1, 3
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV every 8 hours (if local 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

Duration for Severe Infections

• Treat for 7-14 days for severe cellulitis with systemic toxicity, guided by clinical response 1
• For documented necrotizing fasciitis, continue for 7-14 days after surgical debridement 1

Indications for Hospitalization

Hospitalize patients with any of the following 1:

• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Hypotension or hemodynamic instability 1
• Altered mental status or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1

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

Additional Adjunctive Interventions

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates colonization and reduces recurrent infection risk 1
• Address venous insufficiency and lymphedema with compression stockings once acute infection resolves 1
• Treat chronic edema, obesity, and eczema as predisposing conditions 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Special Populations and Scenarios

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg every 6 hours is the optimal choice, providing single-agent coverage for both streptococci and MRSA 1
• Levofloxacin 500 mg daily can be reserved for patients with beta-lactam allergies, though it lacks reliable MRSA coverage 1
• Linezolid 600 mg twice daily covers both streptococci and MRSA but is expensive and typically reserved for complicated cases 1

Pediatric Dosing

• Cephalexin or dicloxacillin: 25-50 mg/kg/day divided every 6 hours 1
• Clindamycin: 10-13 mg/kg/dose every 6-8 hours (if local resistance <10%) 1
• Vancomycin (IV): 15 mg/kg every 6 hours for hospitalized children 1
• Linezolid (IV): 10 mg/kg every 8 hours for children <12 years; 600 mg twice daily for children ≥12 years 1, 3
• Doxycycline: Never use in children <8 years due to tooth discoloration and bone growth effects 1

Diabetic Foot Cellulitis

• Consider broader coverage with amoxicillin-clavulanate, cefuroxime, or fluoroquinolones for moderate diabetic foot infections 1
• Assess for deeper infection or osteomyelitis, which may require prolonged therapy 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 optimal management of risk factors, consider 1:

• Penicillin V 250 mg orally twice daily 1
• Erythromycin 250 mg orally twice daily 1
• Intramuscular benzathine penicillin (monthly) 1

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because community MRSA prevalence is high—beta-lactam monotherapy succeeds in 96% of typical cases 1, 2
• Do not use doxycycline or SMX-TMP as monotherapy for typical cellulitis, as streptococcal coverage will be inadequate 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1
• Do not miss necrotizing fasciitis—look for severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, or bullous changes, and obtain emergent surgical consultation if suspected 1
• Do not forget to assess for abscess—purulent collections require incision and drainage as primary treatment, not antibiotics alone 1

Reassessment and Follow-Up

• Mandatory reassessment in 24-48 hours to verify clinical response 1
• If spreading despite appropriate antibiotics, reassess for MRSA risk factors, necrotizing infection, or misdiagnosis 1
• Transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 1