Treatment of Cellulitis
For typical uncomplicated cellulitis, beta-lactam monotherapy (such as cephalexin, dicloxacillin, or amoxicillin) for 5 days is the standard of care, with a 96% success rate, and MRSA coverage is unnecessary unless specific risk factors are present. 1, 2
First-Line Antibiotic Selection
For outpatient management of uncomplicated cellulitis:
Treatment duration is exactly 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 randomized controlled trial evidence 1.
When to Add MRSA Coverage
MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and empiric MRSA coverage should NOT be added routinely. 1, 2
Add MRSA-active antibiotics ONLY when these specific risk factors are present: 1
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Known MRSA colonization or evidence of MRSA infection elsewhere 1
- Systemic inflammatory response syndrome (SIRS) 1
- Failure to respond to beta-lactam therapy after 48-72 hours 1
When MRSA coverage is needed, use: 1
- Clindamycin monotherapy 300-450 mg orally every 6 hours (provides both streptococcal and MRSA coverage) 1
- Trimethoprim-sulfamethoxazole PLUS a beta-lactam (combination required because TMP-SMX lacks reliable streptococcal activity) 1
- Doxycycline 100 mg twice daily PLUS a beta-lactam (doxycycline alone is inadequate for streptococcal coverage) 1
Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1.
Inpatient/IV Antibiotic Selection
For hospitalized patients with complicated cellulitis requiring IV therapy: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
- Alternative IV agents with equivalent efficacy: 1
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 1
Transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 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
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
- Alternative combinations: 1
Treatment duration for severe infections is 7-14 days, guided by clinical response. 1
Warning signs requiring emergent surgical consultation: 1
- Severe pain out of proportion to examination 1
- Skin anesthesia 1
- Rapid progression despite appropriate antibiotics 1
- Gas in tissue 1
- Bullous changes 1
- "Wooden-hard" subcutaneous tissues 1
Indications for Hospitalization
Hospitalize if ANY of the following are present: 1, 2
- Systemic inflammatory response syndrome (SIRS): fever, tachycardia, tachypnea 1
- Hypotension or hemodynamic instability 1, 2
- Altered mental status or confusion 1, 2
- Severe immunocompromise or neutropenia 1, 2
- Concern for deeper or necrotizing infection 1, 2
- Failure of outpatient treatment 2
Essential Adjunctive Measures
These non-antibiotic interventions are critical and often neglected: 1, 2
- Elevation of the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1, 2
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates colonization and reduces recurrence risk 1, 2
- Address predisposing conditions: 1, 2
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1, 2.
Special Populations and Situations
Bite-associated cellulitis (human or animal):
- Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily as monotherapy provides single-agent coverage for polymicrobial oral flora 1
- Do NOT add TMP-SMX to this regimen 1
Penicillin/cephalosporin allergy:
- Clindamycin 300-450 mg orally every 6 hours is optimal (covers both streptococci and MRSA) 1
- Fluoroquinolones (levofloxacin, moxifloxacin) should be reserved for patients with beta-lactam allergies 1
Pediatric dosing: 1
- Vancomycin 15 mg/kg IV every 6 hours 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
Prevention of Recurrent Cellulitis
Annual recurrence rates are 8-20% in patients with previous leg cellulitis. 1
For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics: 1, 2
- Penicillin V 250 mg orally twice daily 1
- Erythromycin 250 mg orally twice daily 1
- Intramuscular benzathine penicillin 4
Common Pitfalls to Avoid
- Do not reflexively add MRSA coverage simply because the patient is hospitalized or because community MRSA rates are high 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 (e.g., vancomycin PLUS piperacillin-tazobactam) for simple cellulitis; this represents significant overtreatment 1
- Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 1
- Consider ultrasound if there is any clinical uncertainty about abscess, as purulent collections require incision and drainage plus MRSA-active antibiotics 1
- Blood cultures should be obtained in patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1, 2