What is the recommended treatment for cellulitis?

Treatment of Cellulitis

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis and should be your first-line treatment, with oral agents such as cephalexin, dicloxacillin, or amoxicillin for 5 days. 1, 2

First-Line Antibiotic Selection for Uncomplicated Cellulitis

For outpatient management of typical nonpurulent cellulitis:

• Oral beta-lactam monotherapy is successful in 96% of cases because β-hemolytic streptococci and methicillin-sensitive S. aureus are the primary pathogens 1, 3
• Recommended oral agents include:
  • Cephalexin (preferred by many clinicians) 1
  • Dicloxacillin 250-500 mg every 6 hours 1
  • Amoxicillin 1, 2
  • Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily 1
  • Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA if local resistance <10%) 1, 2

Critical point: MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, so routine MRSA coverage is unnecessary and represents overtreatment 1, 2, 4

Treatment Duration

• Treat for 5 days if clinical improvement occurs 1, 2
• Extend treatment only if symptoms have not improved within this 5-day 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 or injection drug use 1
• Purulent drainage or exudate 1
• Evidence of MRSA infection elsewhere or known MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

If MRSA coverage is needed, choose one of these regimens:

• Clindamycin monotherapy 300-450 mg every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole (Bactrim) PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1

Common pitfall: Never use doxycycline or Bactrim as monotherapy for typical cellulitis—their activity against β-hemolytic streptococci is unreliable 1, 4

Inpatient/IV Antibiotic Management

For hospitalized patients requiring IV therapy:

Uncomplicated cellulitis without MRSA risk factors:

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

Complicated cellulitis or MRSA coverage needed:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1
• Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 1, 5
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV every 8 hours (if local MRSA resistance <10%) 1

Severe cellulitis with systemic toxicity or suspected necrotizing fasciitis:

• 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: vancomycin plus a carbapenem, or vancomycin plus ceftriaxone and metronidazole 1
• For documented group A streptococcal necrotizing fasciitis: penicillin plus clindamycin 1

Treatment duration for severe infections: 7-14 days guided by clinical response 1

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 1
• Hypotension or hemodynamic instability 1
• Altered mental status or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1

Adjunctive Measures

These interventions accelerate recovery and prevent recurrence: 1, 2

• Elevate the affected extremity to promote gravitational drainage of edema 1, 2
• Examine and treat interdigital toe spaces for tinea pedis, fissuring, or maceration 1, 2
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, eczema 1, 2, 6
• Consider systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 2

Special Situations

Bite-associated cellulitis (human or animal):

• Amoxicillin-clavulanate 875/125 mg twice daily as monotherapy (provides polymicrobial coverage) 1
• Do NOT add Bactrim to this regimen 1

Penicillin allergy:

• Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA) 1
• Cefuroxime 500 mg twice daily if only mild penicillin allergy 1

Pediatric dosing:

• Cephalexin or clindamycin at weight-based doses 1
• Vancomycin 15 mg/kg IV every 6 hours for hospitalized children 1
• Never use doxycycline in children <8 years due to tooth discoloration 1

Reassessment and Treatment Failure

Mandatory reassessment at 48-72 hours to verify clinical response: 1

• If spreading despite appropriate antibiotics, consider:
  • MRSA involvement (switch to vancomycin or add MRSA coverage) 1
  • Necrotizing fasciitis (obtain emergent surgical consultation) 1
  • Misdiagnosis (consider pseudocellulitis: venous stasis dermatitis, contact dermatitis, DVT) 4
  • Abscess requiring drainage 1

Do not continue ineffective antibiotics beyond 48 hours—progression indicates either resistant organisms or a different/deeper infection 1