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 should be used in 96% of cases, as MRSA coverage is unnecessary for nonpurulent cellulitis without specific risk factors. 1

Recommended Oral Regimens for Uncomplicated Cellulitis

• Cephalexin 500 mg orally four times daily for 5 days 1, 2
• Dicloxacillin 250-500 mg orally every 6 hours for 5 days 1, 2
• Amoxicillin 500 mg orally three times daily for 5 days 1, 2
• Penicillin V 250-500 mg orally four times daily for 5 days 2
• Clindamycin 300-450 mg orally every 6 hours for 5 days (covers both streptococci and MRSA, useful for penicillin allergy) 1, 2

The evidence is clear: beta-lactam antibiotics successfully treat typical cellulitis in 96% of patients because the causative organisms are predominantly β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, not MRSA. 1, 3

Treatment Duration

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

This represents a major shift from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 1 Mandatory reassessment at 24-48 hours is critical to verify clinical response. 1

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 3

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1, 3
• Systemic inflammatory response syndrome (SIRS) 1
• Failure of beta-lactam therapy after 48 hours 1
• Athletes, prisoners, military recruits, long-term care residents, men who have sex with men 3

MRSA-Active Regimens When Indicated

For purulent cellulitis requiring MRSA coverage: 1

• Clindamycin monotherapy 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (e.g., TMP-SMX 1-2 double-strength tablets twice daily plus cephalexin 500 mg four times daily) 1
• Doxycycline PLUS a beta-lactam (doxycycline 100 mg twice daily plus cephalexin 500 mg four times daily) 1

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against β-hemolytic streptococci is unreliable. 1, 2 Clindamycin is the only oral agent that can be used alone for MRSA coverage while maintaining streptococcal activity. 1

Inpatient Management

Indications for Hospitalization

Hospitalize patients with any of the following: 1, 2

• Systemic inflammatory response syndrome (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 necrotizing fasciitis or deeper infection 1, 2
• Failure of outpatient therapy 2

IV Antibiotic Selection for Hospitalized Patients

For uncomplicated cellulitis requiring hospitalization (no MRSA risk factors): 1

• Cefazolin 1-2 g IV every 8 hours (preferred) 1
• Oxacillin 2 g IV every 6 hours (alternative) 1

For complicated cellulitis or when MRSA coverage is needed: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 2
• 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%, 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, 2

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• 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

For documented group A streptococcal necrotizing fasciitis: Penicillin PLUS clindamycin is the specific recommended combination. 1

Treatment duration for severe infections is 7-14 days, guided by clinical response and source control. 1

Warning Signs of Necrotizing Fasciitis

Obtain emergent surgical consultation if any of the following are present: 1

• Severe pain out of proportion to examination 1
• Skin anesthesia or numbness 1
• Rapid progression despite antibiotics 1
• Gas in tissue (crepitus) 1
• Bullous changes 1
• Systemic toxicity with hypotension 1

These infections progress rapidly and require immediate surgical debridement in addition to antibiotics. 1

Adjunctive Measures

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

Additional measures to prevent recurrence: 1, 2

• Examine interdigital toe spaces for tinea pedis and treat toe web abnormalities 1, 2
• Address predisposing conditions including edema, venous insufficiency, lymphedema, obesity, and eczema 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Special Populations and Scenarios

Bite-Associated Cellulitis

Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily is the preferred monotherapy for animal or human bite-associated cellulitis, providing single-agent coverage for polymicrobial oral flora. 1 Do not add TMP-SMX to this regimen. 1

Penicillin Allergy

For patients with penicillin allergy: 1

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA) 1
• Levofloxacin 500 mg daily (reserve for beta-lactam allergies, 5-day course as effective as 10 days) 1

Cephalosporin Allergy

For patients with cephalosporin allergy but mild penicillin allergy: 1

• Penicillin V 250-500 mg orally four times daily 1
• Clindamycin 300-450 mg orally every 6 hours 1

Pediatric Dosing

For hospitalized children with complicated cellulitis: 1

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

For children requiring MRSA coverage: Doxycycline 2 mg/kg/dose orally every 12 hours (only for children >8 years and <45 kg) PLUS a beta-lactam. 1 Never use doxycycline in children under 8 years due to tooth discoloration and bone growth effects. 1

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or in a high-prevalence setting—MRSA is uncommon in typical nonpurulent cellulitis even in hospitals with high MRSA rates. 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection. 1
• Do not use combination therapy (vancomycin plus piperacillin-tazobactam) for simple cellulitis—this represents significant overtreatment and should be reserved for life-threatening infections or suspected necrotizing fasciitis. 1
• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not antibiotics alone. 1
• Distinguish cellulitis from purulent collections (furuncles, abscesses, septic bursitis)—purulent collections require drainage as primary treatment, with antibiotics having a subsidiary role. 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 Options include cephalexin, dicloxacillin, or clindamycin for continued MRSA coverage. 1

Prevention of Recurrence

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

• Oral penicillin or erythromycin 2
• Intramuscular benzathine penicillin 2