Treatment of Cellulitis
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis and is successful in 96% of patients—MRSA coverage is unnecessary in most cases. 1
First-Line Antibiotic Selection
For typical nonpurulent cellulitis without systemic signs, beta-lactam antibiotics targeting streptococci are the cornerstone of treatment:
- Cephalexin (most commonly used)
- Dicloxacillin 250-500 mg every 6 hours
- Amoxicillin
- Amoxicillin-clavulanate (Augmentin)
- Penicillin
Intravenous options for hospitalized patients: 1
- Cefazolin 1-2 g IV every 8 hours (preferred IV beta-lactam)
- Oxacillin
The Infectious Diseases Society of America emphasizes that MRSA is an uncommon cause of typical cellulitis, even in hospitals with high MRSA prevalence, so reflexive addition of MRSA coverage is inappropriate. 1, 2, 3, 4
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 2 This represents a significant departure from traditional 7-14 day courses and is supported by high-quality evidence showing equivalent outcomes with shorter duration therapy. 1
When to Add MRSA Coverage
MRSA-active antibiotics should be added only when specific risk factors are present: 1, 2
- Penetrating trauma or injection drug use
- Purulent drainage or exudate
- Evidence of MRSA infection elsewhere or known MRSA colonization
- Systemic inflammatory response syndrome (SIRS)
- Failure to respond to beta-lactam therapy after 48-72 hours
MRSA-active regimens when indicated: 1
- Clindamycin monotherapy 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy if local resistance <10%)
- Doxycycline 100 mg twice daily PLUS a beta-lactam (doxycycline alone is inadequate due to unreliable streptococcal coverage)
- Trimethoprim-sulfamethoxazole PLUS a beta-lactam (same rationale—never use as monotherapy)
Critical pitfall: Combination therapy with trimethoprim-sulfamethoxazole plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 1 Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 1
Inpatient/Severe Cellulitis Management
For hospitalized patients requiring IV therapy, the approach depends on severity:
Uncomplicated cellulitis requiring hospitalization: 1
- Cefazolin 1-2 g IV every 8 hours remains appropriate if nonpurulent and lacking MRSA risk factors
- Success rate of 96% with beta-lactam monotherapy applies even in inpatient settings 1
Complicated cellulitis or MRSA risk factors: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence)
- Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence)
- Daptomycin 4 mg/kg IV once daily (A-I evidence)
- Clindamycin 600 mg IV every 8 hours (if local MRSA resistance <10%)
Severe cellulitis with systemic toxicity or suspected necrotizing fasciitis: 1
Broad-spectrum combination therapy is mandatory:
- Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours
- Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours)
- Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours
For documented group A streptococcal necrotizing fasciitis specifically: Penicillin plus clindamycin is the recommended combination. 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 Appropriate oral options include cephalexin, dicloxacillin, or clindamycin (if MRSA coverage needed). 1
Adjunctive Measures
Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2 This simple intervention should be implemented in all cases.
Treat predisposing conditions: 1, 2
- Tinea pedis and toe web abnormalities
- Venous insufficiency and lymphedema
- Chronic edema
- Eczema and venous stasis dermatitis
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1, 2
Indications for Hospitalization
Admit patients with any of the following: 1, 2
- Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm
- Hypotension or hemodynamic instability
- Altered mental status or confusion
- Severe immunocompromise or neutropenia
- Concern for necrotizing infection or deeper involvement
- Failure of outpatient treatment
Special Populations
Pediatric dosing: 1
- Vancomycin 15 mg/kg IV every 6 hours (first-line for hospitalized children)
- Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if stable, no bacteremia, local resistance <10%)
- Linezolid 600 mg IV twice daily (>12 years) or 10 mg/kg/dose IV every 8 hours (<12 years)
Penicillin-allergic patients: 1
- Clindamycin 300-450 mg orally every 6 hours is ideal as it covers both streptococci and MRSA without requiring combination therapy
Common Pitfalls to Avoid
Do not routinely add MRSA coverage for typical cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1
Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
Reassess at 48-72 hours to verify clinical response—treatment failure rates of 21% have been reported with some regimens, and progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection. 1
Evaluate for necrotizing fasciitis if severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, systemic toxicity, or bullous changes are present—obtain emergent surgical consultation. 1
Distinguish cellulitis from purulent collections (abscesses, furuncles)—purulent collections require incision and drainage as primary treatment, with antibiotics playing a subsidiary role. 1