Treatment of Cellulitis
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 5-day treatment duration if clinical improvement occurs. 1
First-Line Antibiotic Selection
For uncomplicated, non-purulent cellulitis, use beta-lactam monotherapy—MRSA coverage is unnecessary and represents overtreatment. 1, 2
Oral Options for Outpatient Treatment
- Cephalexin (first-generation cephalosporin) 1, 2
- Dicloxacillin 250-500 mg every 6 hours 1
- Amoxicillin 1, 2
- Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily—particularly appropriate for bite-associated cellulitis 1
- Penicillin 1, 2
Beta-lactam therapy succeeds in 96% of cellulitis cases, confirming that routine MRSA coverage is unnecessary. 1 This high success rate holds true even in settings with high community MRSA prevalence, because MRSA is an uncommon cause of typical non-purulent cellulitis. 1, 3
Intravenous Options for Hospitalized Patients
- Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 1
- Oxacillin 2 g IV every 6 hours 1
Critical pitfall: Do not reflexively add MRSA coverage simply because a patient is hospitalized—beta-lactam monotherapy remains appropriate for non-purulent cellulitis without specific MRSA risk factors, even in the inpatient setting. 1
Treatment Duration
Treat for 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2 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 1, 2
- Purulent drainage or exudate 1, 2
- Injection drug use 1, 2
- Evidence of MRSA infection elsewhere or documented MRSA colonization 1
- Systemic inflammatory response syndrome (SIRS) 1
MRSA-Active Regimens
For purulent cellulitis requiring MRSA coverage:
- Clindamycin monotherapy 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline lacks reliable streptococcal coverage and must never be used as monotherapy) 1
- Trimethoprim-sulfamethoxazole (SMX-TMP) PLUS a beta-lactam 1
Critical caveat: Doxycycline and SMX-TMP have unreliable activity against beta-hemolytic streptococci and must be combined with a beta-lactam when treating typical cellulitis. 1 Using these agents as monotherapy for non-purulent cellulitis will result in inadequate streptococcal coverage. 1
Severe Cellulitis Requiring Hospitalization
For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use mandatory broad-spectrum combination therapy: 1
IV Combination Regimens
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
- Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 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
Alternative MRSA-Active IV Agents
- Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1
- Linezolid 600 mg IV twice daily (A-I evidence) 1, 4
- Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
- Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%, A-III evidence) 1
- Telavancin 10 mg/kg IV once daily (A-I evidence) 1
Treatment duration for severe infections: 7-14 days guided by clinical response, with reassessment at 5 days. 1
Special Considerations
Penicillin Allergy
For patients allergic to penicillin, use clindamycin 300-450 mg orally every 6 hours for 5 days. 1 Clindamycin provides coverage for both streptococci and MRSA without requiring combination therapy. 1
Pediatric Dosing
- Vancomycin 15 mg/kg IV every 6 hours (first-line for hospitalized children) 1
- Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if stable, no bacteremia, local resistance <10%) 1
- Linezolid 10 mg/kg/dose IV every 8 hours for children <12 years; 600 mg IV twice daily for children ≥12 years 1
- Doxycycline 2 mg/kg/dose orally every 12 hours (only for children >8 years and <45 kg; never use in children <8 years due to tooth discoloration) 1
Necrotizing Fasciitis
For documented group A streptococcal necrotizing fasciitis, use penicillin plus clindamycin. 1 Emergent surgical consultation and debridement are mandatory. 1
Adjunctive Measures
- Elevate the affected extremity to promote drainage and hasten improvement 1, 2
- Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, obesity 1, 2, 5
- Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1, 2
Hospitalization Criteria
Hospitalize patients with: 1, 2
- Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
- Hypotension, confusion, or altered mental status 1
- Severe immunocompromise or neutropenia 1
- Concern for necrotizing infection or deeper involvement 1, 2
- Failure of outpatient treatment 2
Treatment Failure
If cellulitis spreads despite appropriate antibiotics within 24-48 hours, reassess for: 1
- Necrotizing fasciitis warning signs: severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes 1
- MRSA involvement (switch to vancomycin or linezolid) 1
- Misdiagnosis (consider pseudocellulitis: venous stasis dermatitis, contact dermatitis, DVT) 6
- Abscess requiring drainage (obtain ultrasound if clinical uncertainty) 1
Never continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection. 1
Transition to Oral Therapy
Transition from IV 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