What is the recommended treatment for cellulitis?

Treatment of Cellulitis

First-Line Antibiotic Selection

For typical nonpurulent cellulitis, beta-lactam monotherapy is the standard of care and is successful in 96% of patients—MRSA coverage is NOT routinely necessary. 1, 2

Oral Regimens for Uncomplicated Cellulitis

• Cephalexin 500 mg orally four times daily is the preferred first-line agent 1
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and MSSA coverage 2
• Alternative beta-lactams include penicillin, amoxicillin, or amoxicillin-clavulanate 1, 2
• Clindamycin 300-450 mg orally four times daily is appropriate for penicillin-allergic patients, covering both streptococci and MRSA 1, 2

Intravenous Regimens for Hospitalized Patients

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 2
• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis or when MRSA coverage is needed (A-I evidence) 1, 2
• Alternative MRSA-active agents include linezolid 600 mg IV twice daily (A-I evidence), daptomycin 4 mg/kg IV once daily (A-I evidence), or clindamycin 600 mg IV every 8 hours if local resistance <10% 1, 2

Treatment Duration

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

• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• For complicated infections requiring hospitalization, 7-14 days may be appropriate, guided by clinical response 1
• Patients should demonstrate clinical improvement within 24-48 hours of starting appropriate antibiotics 1

When to Add MRSA Coverage

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

Specific MRSA Risk Factors:

• Penetrating trauma 1, 2
• Purulent drainage or exudate 1, 2
• Injection drug use 1, 2
• Evidence of MRSA infection elsewhere or nasal MRSA colonization 1, 2
• Systemic inflammatory response syndrome (SIRS) 1, 2
• Athletes, prisoners, military recruits, residents of long-term care facilities 3

MRSA-Active Regimens:

• Clindamycin 300-450 mg orally four times daily provides single-agent coverage for both streptococci and MRSA (only if local resistance <10%) 1, 2
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., cephalexin) 1, 2
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1, 2

Critical Pitfall: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis—their activity against beta-hemolytic streptococci is unreliable. 1, 2

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, 2

Combination Regimens for Severe Infection:

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

Warning Signs Requiring Emergent Surgical Consultation:

• Severe pain out of proportion to examination 1
• Skin anesthesia or rapid progression 1
• Gas in tissue or bullous changes 1
• Systemic toxicity (fever, hypotension, altered mental status) 1

For documented group A streptococcal necrotizing fasciitis, use penicillin plus clindamycin specifically. 2

Indications for Hospitalization

Hospitalize patients with any of the following: 1, 2

• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Hypotension or hemodynamic instability 1, 2
• Altered mental status or confusion 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for deeper or necrotizing infection 1, 2
• Failure of outpatient treatment 1

Adjunctive Measures

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

Additional Supportive Care:

• Treat predisposing conditions: tinea pedis, venous eczema, chronic edema, trauma 1, 2
• Examine interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens 1, 2
• Keep skin well hydrated with emollients 1
• Consider compression stockings or diuretic therapy for underlying edema 1

Corticosteroids:

• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients to reduce inflammation, though evidence is limited (weak recommendation, moderate evidence) 1, 2
• One small study showed that adding NSAIDs (ibuprofen 400 mg every 6 hours for 5 days) significantly shortened time to resolution 4

Diagnostic Testing

Blood cultures are NOT routinely recommended for typical cellulitis. 1

Obtain Blood Cultures When:

• Malignancy or severe immunocompromise 1
• Severe systemic features or neutropenia 1
• Unusual predisposing factors 1

Use point-of-care ultrasound if there is clinical uncertainty about abscess formation—purulent collections require incision and drainage, not antibiotics alone. 1, 5

Special Clinical Scenarios

Bite-Associated Cellulitis:

• Amoxicillin-clavulanate 875/125 mg twice daily provides single-agent coverage for polymicrobial oral flora 1, 2
• Do not add trimethoprim-sulfamethoxazole to this regimen 2

Cellulitis Failing Initial Therapy:

• Reassess for MRSA risk factors, necrotizing infection, or misdiagnosis 1
• Switch to vancomycin or linezolid if MRSA suspected or systemic toxicity present 1
• Do not continue ineffective antibiotics beyond 48 hours 1
• Obtain emergent surgical consultation if any signs of necrotizing infection 1

Prevention of Recurrence:

• Each episode causes lymphatic damage and increases risk of future episodes 1
• For frequent recurrences despite preventive measures, consider prophylactic antibiotics: monthly intramuscular benzathine penicillin or oral penicillin V/erythromycin twice daily 1

Common Pitfalls to Avoid

• Do not add MRSA coverage reflexively—even in hospitals with high MRSA prevalence, MRSA is uncommon in typical cellulitis 1, 2
• Do not use combination therapy when monotherapy is appropriate—this increases adverse effects without improving outcomes 2
• Do not miss an abscess—if fluctuance is present, drainage is primary treatment, not antibiotics 1, 5
• Do not delay surgical consultation if necrotizing infection is suspected—these progress rapidly and require debridement 1
• Do not treat for 10-14 days routinely—5 days is sufficient if clinical improvement occurs 1, 2