Treatment of Cellulitis
First-Line Antibiotic Therapy
For typical uncomplicated cellulitis without purulent drainage, beta-lactam monotherapy is the standard of care and is successful in 96% of patients—MRSA coverage is NOT routinely necessary. 1
Recommended Oral Beta-Lactam Agents
- Cephalexin (most commonly used first-line agent) 1
- Dicloxacillin 250-500 mg every 6 hours 1
- Amoxicillin 1
- Amoxicillin-clavulanate 1
- Penicillin 1
All provide adequate coverage against β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, which are the causative organisms in the 15% of cases where pathogens are identified. 2
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 3, 1 This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 1
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present: 3, 1
- Penetrating trauma 3, 1
- Purulent drainage or exudate 3, 1
- Injection drug use 3, 1
- Evidence of MRSA infection elsewhere or nasal MRSA colonization 3, 1
- Systemic inflammatory response syndrome (SIRS) 3
- Athletes, prisoners, military recruits, residents of long-term care facilities 2
MRSA-Active Regimens for Outpatients
When MRSA coverage is needed, use one of these options: 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., cephalexin) 1
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
Critical pitfall: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against β-hemolytic streptococci is unreliable. 1
Inpatient Management and IV Antibiotics
Indications for Hospitalization
Admit patients with any of the following: 3, 1
- SIRS (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm) 1
- Hypotension or hemodynamic instability 3
- Altered mental status or confusion 3, 1
- Severe immunocompromise or neutropenia 1
- Concern for deeper or necrotizing infection 3
IV Antibiotic Selection
For uncomplicated cellulitis requiring hospitalization (without MRSA risk factors):
- Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1
- Oxacillin 2 g IV every 6 hours is an alternative 3
For complicated cellulitis with MRSA risk factors or purulent features:
- Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 4
- Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 1, 4
- 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 Cellulitis with Systemic Toxicity
For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: 3, 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 3, 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
Duration for severe infections: 7-14 days guided by clinical response, not the standard 5 days. 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 step-down options include: 1
- Cephalexin
- Dicloxacillin
- Clindamycin (if continued MRSA coverage needed)
Adjunctive Measures
These non-antibiotic interventions hasten improvement and reduce recurrence risk: 3, 1
- Elevation of the affected extremity promotes gravitational drainage of edema 3, 1
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrent infection 3, 1
- Address predisposing conditions: edema, venous insufficiency, lymphedema, obesity, eczema 1
- Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1
Common Pitfalls to Avoid
Do not reflexively add MRSA coverage for typical nonpurulent cellulitis simply because the patient is hospitalized or in a high-MRSA-prevalence setting—beta-lactam monotherapy succeeds in 96% of cases. 1
Do not confuse cellulitis with purulent collections (abscesses, furuncles)—these require incision and drainage as primary treatment, not antibiotics alone. 1
Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection requiring reassessment. 1
Assess for warning signs of necrotizing fasciitis: severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, bullous changes—these require emergent surgical consultation. 1