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
• 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

Indications for Hospitalization

Hospitalize if any of the following are present: 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 gravitational 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, 4
• One small study showed that adding ibuprofen 400 mg every 6 hours for 5 days significantly shortened time to resolution 4

Special Populations and Scenarios

Bite-Associated Cellulitis:

• Amoxicillin-clavulanate 875/125 mg twice daily provides single-agent coverage for polymicrobial oral flora from human or animal bites 1, 2

Pediatric Dosing:

• Vancomycin 15 mg/kg IV every 6 hours for hospitalized children 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (only if stable, no bacteremia, 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
• Doxycycline 2 mg/kg/dose orally every 12 hours for children >8 years and <45 kg 1

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

Recurrent Cellulitis Prevention:

• Each attack causes lymphatic inflammation and possibly permanent damage, potentially leading to lymphedema 1
• For frequent infections despite preventive measures, prophylactic antibiotics may be reasonable: monthly intramuscular benzathine penicillin or oral erythromycin/penicillin V twice daily 1

Common Diagnostic Pitfalls

Blood cultures are not routinely recommended for typical cellulitis, but should be obtained for patients with malignancy, severe systemic features, unusual predisposing factors, or immunocompromise. 1

Distinguish cellulitis from purulent collections (abscesses, furuncles): 1

• Cellulitis requires antibiotics as primary treatment 1
• Purulent collections require incision and drainage, with antibiotics having a subsidiary role 1, 5
• Use point-of-care ultrasound if clinical uncertainty exists 1, 5

Treatment Failure Algorithm

If cellulitis is spreading despite appropriate antibiotics after 24-48 hours: 1

1. Reassess for necrotizing fasciitis warning signs (obtain emergent surgical consultation if suspected) 1
2. Evaluate for MRSA risk factors and switch to vancomycin or linezolid if indicated 1
3. Consider misdiagnosis (mimics include venous stasis dermatitis, contact dermatitis, deep vein thrombosis) 3, 6
4. Assess for underlying complicating conditions: immunosuppression, chronic liver disease, chronic kidney disease 3

Never continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection than initially recognized. 1, 3