What is the recommended treatment for cellulitis?

Treatment of Cellulitis

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

First-Line Antibiotic Selection

For typical nonpurulent cellulitis, use a single beta-lactam antibiotic targeting streptococci and methicillin-sensitive Staphylococcus aureus. 1

Oral Options (Outpatient)

• Cephalexin 500 mg every 6 hours is the preferred first-line agent 1, 2
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and MSSA coverage 1, 2
• Amoxicillin or penicillin are acceptable alternatives 1
• Amoxicillin-clavulanate 875/125 mg twice daily for bite-associated cellulitis or when beta-lactamase-producing organisms are suspected 1, 2

IV Options (Inpatient)

• Cefazolin 1-2 g IV every 8 hours is the preferred parenteral agent for hospitalized patients 1, 2
• Nafcillin is an alternative for severe cases 2
• Oxacillin can be used for uncomplicated cellulitis requiring hospitalization 1

Penicillin Allergy

• Clindamycin 300-450 mg orally every 6 hours covers both streptococci and MRSA, eliminating the need for combination therapy 1, 2
• 99.5% of Streptococcus pyogenes strains remain susceptible to clindamycin 2

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 3, 2

• Five-day courses are as effective as 10-day courses for uncomplicated cellulitis 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• Reassess within 24-48 hours for outpatients to ensure clinical improvement 2

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

High-Risk Features Requiring MRSA Coverage

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate visible 1, 2
• Evidence of MRSA infection elsewhere or known nasal colonization 1, 2
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, hypotension, or altered mental status 1, 2
• Failure to respond to beta-lactam therapy after 48-72 hours 1, 2

MRSA Coverage Options

Oral regimens when MRSA coverage is needed: 1

• Clindamycin 300-450 mg three times daily (monotherapy covering both streptococci and MRSA) 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 DS tablets twice daily PLUS a beta-lactam (cephalexin, penicillin, or amoxicillin) 1, 2
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1, 2

IV regimens for hospitalized patients with complicated cellulitis: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 2
• Linezolid 600 mg IV twice daily (A-I evidence) 1, 2
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1, 2
• Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%, A-III evidence) 1, 2

Critical Caveat

Never use TMP-SMX or doxycycline as monotherapy for typical cellulitis—these agents lack reliable activity against beta-hemolytic streptococci and must be combined with a beta-lactam. 1, 2

Severe Cellulitis with Systemic Toxicity

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use mandatory broad-spectrum combination therapy: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1, 2
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1
• Duration: 7-14 days guided by clinical response 1

Warning Signs of Necrotizing Fasciitis

Obtain emergent surgical consultation if any of these are present: 1

• Severe pain out of proportion to examination 1
• Skin anesthesia, rapid progression, or gas in tissue 1
• Bullous changes or systemic toxicity 1

Hospitalization Criteria

Admit patients with any of the following: 2

• SIRS criteria (fever, altered mental status, hemodynamic instability) 2
• Concern for deeper or necrotizing infection 2
• Poor adherence to outpatient therapy 2
• Severe immunocompromise or neutropenia 1, 2
• Failure of outpatient treatment after 24-48 hours 2

Adjunctive Measures

Essential non-antibiotic interventions that hasten improvement: 1, 3, 2

• Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances 1, 3, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat if present 2
• Treat predisposing conditions: venous insufficiency, lymphedema, eczema, obesity, chronic edema 1, 3, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults only—avoid in diabetic patients 1, 2

Special Populations

Pediatric Dosing

• Vancomycin 15 mg/kg IV every 6 hours (first-line for hospitalized children) 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (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 (only for children >8 years and <45 kg) 1
• Never use doxycycline in children under 8 years due to tooth discoloration and bone growth effects 1

Diabetic Patients

• Require longer treatment duration compared to non-diabetic patients 2
• Avoid systemic corticosteroids despite evidence showing benefit in non-diabetics 2
• Elevation of affected extremity is especially important 2

Treatment Failure Algorithm

If no improvement after 48-72 hours of appropriate first-line antibiotics: 2

1. Add empiric MRSA coverage immediately (TMP-SMX, doxycycline, or clindamycin as above) 2
2. Assess for abscess requiring drainage using ultrasound if clinically uncertain 1
3. Consider alternative diagnoses: deep vein thrombosis, necrotizing infection, or cellulitis mimickers 2
4. Obtain blood cultures and wound culture if any drainage present 2
5. If systemic signs or rising WBC, hospitalize and start IV vancomycin 2

Antibiotics without CA-MRSA activity have 4.22 times higher odds of treatment failure (95% CI 2.25-7.92) in MRSA-prevalent areas when MRSA is the causative organism. 2

Recurrent Cellulitis Prevention

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

• Oral penicillin or erythromycin twice daily for 4-52 weeks 2
• Intramuscular benzathine penicillin every 2-4 weeks 2

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical cellulitis—MRSA is an uncommon cause even in hospitals with high MRSA prevalence 1, 2
• Do not use combination therapy when monotherapy is appropriate—this increases adverse effects without improving outcomes 1
• Do not obtain blood cultures for typical cellulitis—positive in only 5% of cases; reserve for severe systemic features, malignancy, neutropenia, or unusual predisposing factors 2
• Do not delay switching therapy beyond 48-72 hours of failed treatment—increases morbidity 2
• Do not extend treatment beyond 5 days automatically—only extend if clinical improvement has not occurred 2