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 is successful in 96% of patients—MRSA coverage is NOT routinely necessary. 1

Oral Antibiotic Options for Outpatient Management

For typical nonpurulent cellulitis without systemic signs of infection, the following oral agents provide adequate streptococcal and methicillin-sensitive S. aureus coverage:

• Penicillin, amoxicillin, or amoxicillin-clavulanate 1
• Dicloxacillin 250-500 mg every 6 hours 1
• Cephalexin (first-generation cephalosporin) 1
• Cefuroxime 500 mg twice daily 1
• Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA, useful for penicillin-allergic patients) 1

The evidence strongly supports that MRSA is an uncommon cause of typical cellulitis, even in hospitals with high MRSA prevalence, so reflexive addition of MRSA coverage represents overtreatment. 1, 2

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

When to Add MRSA Coverage

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

• 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) with fever, tachycardia, or hypotension 1
• Failure to respond to beta-lactam therapy after 48 hours 1

MRSA-Active Regimens for Outpatient Use

When MRSA coverage is indicated:

• Clindamycin monotherapy 300-450 mg every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole (SMX-TMP) PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1

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

Intravenous Therapy for Hospitalized Patients

Indications for Hospitalization

Admit patients with any of the following: 1

• Systemic toxicity: SIRS, fever >38°C, hypotension, tachycardia >90 bpm, altered mental status 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing fasciitis: severe pain out of proportion to exam, skin anesthesia, rapid progression, bullous changes, gas in tissue 1

IV Antibiotic Selection

For uncomplicated cellulitis requiring hospitalization (nonpurulent, no MRSA risk factors):

• Cefazolin 1-2 g IV every 8 hours (preferred IV beta-lactam) 1
• Nafcillin or oxacillin 3

For complicated cellulitis or when MRSA coverage is needed:

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

Severe Infections Requiring Broad-Spectrum Coverage

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

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 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, use penicillin plus clindamycin specifically. 1

Duration for severe infections is 7-14 days, guided by clinical response and source control. 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 oral cephalexin, dicloxacillin, or clindamycin for continued coverage. 1

Adjunctive Measures

Beyond antibiotics, the following interventions hasten improvement:

• Elevation of the affected extremity to promote gravity drainage of edema 1
• Treat predisposing conditions: tinea pedis and toe web abnormalities, venous insufficiency, lymphedema, chronic edema 1, 4
• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1

Pediatric Considerations

For hospitalized children with complicated cellulitis:

• Vancomycin 15 mg/kg IV every 6 hours (first-line) 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

For oral therapy in children over 8 years: Doxycycline 2 mg/kg/dose every 12 hours (never use in children under 8 years due to tooth discoloration). 1

Special Situations

Bite-Associated Cellulitis

For human or animal bites, use amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily, which provides single-agent coverage for both streptococci and common oral flora. 1

Penicillin-Allergic Patients

Clindamycin 300-450 mg every 6 hours is ideal, as it covers both streptococci and MRSA without requiring combination therapy. 1

Recurrent Cellulitis

For patients with frequent episodes despite management of underlying conditions, consider prophylactic antibiotics: 3, 4

• Oral penicillin or erythromycin 3
• Intramuscular benzathine penicillin 3

Critical Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases resistance. 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a deeper/different infection. 1
• Do not delay surgical consultation if any signs of necrotizing infection are present, as these progress rapidly and require debridement. 1
• Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens. 1
• Assess for abscess with ultrasound if there is clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not antibiotics alone. 1