What is the recommended treatment for cellulitis?

Cellulitis Treatment

For typical uncomplicated cellulitis, beta-lactam monotherapy (such as cephalexin, dicloxacillin, or amoxicillin) for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1

First-Line Antibiotic Selection

Oral Therapy for Uncomplicated Cellulitis

• Recommended oral agents include: 1, 2

  • Cephalexin 500 mg four times daily 1
  • Dicloxacillin 250-500 mg every 6 hours 1
  • Amoxicillin (standard dosing) 1
  • Penicillin V 250-500 mg four times daily 1
  • Amoxicillin-clavulanate 875/125 mg twice daily 1

• Beta-lactam monotherapy is successful in 96% of patients, confirming that MRSA coverage is unnecessary in typical cases 1, 3

Intravenous Therapy for Hospitalized Patients

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 1
• Alternative IV options include nafcillin 2 g IV every 6 hours or oxacillin 2 g IV every 6 hours 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2 This represents a major shift from traditional 7-14 day courses and is supported by high-quality randomized controlled trial evidence 1

When to Add MRSA Coverage

Specific Risk Factors Requiring MRSA-Active Therapy

Add MRSA coverage ONLY when the following are present: 1, 2

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or concurrent MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA-Active Regimens

For outpatient purulent cellulitis requiring MRSA coverage: 1

• Clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, avoiding need for combination therapy) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline lacks reliable streptococcal activity and must never be used as monotherapy) 1
• Trimethoprim-sulfamethoxazole (SMX-TMP) PLUS a beta-lactam (SMX-TMP alone is inadequate for streptococcal coverage) 1

For hospitalized patients with complicated cellulitis: 1

• 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 every 8 hours (only if local MRSA resistance <10%, A-III evidence) 1

Severe Cellulitis with Systemic Toxicity

Indications for Broad-Spectrum Combination Therapy

Mandatory broad-spectrum combination therapy is required for: 1, 2

• Signs of systemic toxicity (fever, hypotension, tachycardia, altered mental status) 1
• Rapid progression of infection 1
• Suspected necrotizing fasciitis 1
• "Wooden-hard" subcutaneous tissues 1

Recommended IV Combination Regimens

Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS one of the following: 1

• Piperacillin-tazobactam 3.375-4.5 g IV every 6 hours (preferred for polymicrobial coverage) 1
• Carbapenem (meropenem 1 g IV every 8 hours) 1
• Ceftriaxone 2 g IV daily plus metronidazole 500 mg IV every 8 hours 1

Treatment duration for severe infections: 7-14 days, guided by clinical response and source control 1

Critical Pitfalls to Avoid

Common Errors in Management

• Do NOT reflexively add MRSA coverage simply because the patient is hospitalized - MRSA is uncommon in typical cellulitis even in high-prevalence settings 1
• Do NOT use doxycycline or SMX-TMP as monotherapy - these lack reliable streptococcal activity 1
• Do NOT continue ineffective antibiotics beyond 48 hours - progression despite appropriate therapy indicates resistant organisms or deeper infection 1
• Do NOT delay surgical consultation if necrotizing infection is suspected - these progress rapidly and require emergent debridement 1

Distinguishing Cellulitis from Abscess

• Any fluctuant collection requires incision and drainage as primary treatment, with antibiotics playing only a subsidiary role 1, 5
• Use ultrasound if clinical uncertainty exists about presence of abscess 1

Essential Adjunctive Measures

Non-Antibiotic Interventions

• Elevate 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, maceration) and treat to eradicate colonization and reduce recurrence 1, 2
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, eczema 1, 2

Corticosteroid Consideration

• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults to reduce inflammation, though evidence is limited 1, 2

Hospitalization Criteria

Admit patients with any of the following: 1, 2

• Systemic inflammatory response syndrome (SIRS) 1
• Hypotension or hemodynamic instability 1
• Altered mental status or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1
• Failure of outpatient treatment 2

Prevention of Recurrent Cellulitis

Risk Reduction Strategies

• Annual recurrence rates are 8-20% in patients with previous leg cellulitis 1
• Treat all predisposing conditions: tinea pedis, venous insufficiency, lymphedema, toe web abnormalities 1, 2
• Consider compression stockings for venous insufficiency once acute infection resolves 1

Prophylactic Antibiotics

For patients with 3-4 episodes per year despite treating predisposing factors, consider: 1, 2

• Penicillin V 250 mg orally twice daily 1
• Erythromycin 250 mg orally twice daily 1
• Intramuscular benzathine penicillin (for preseptal cellulitis) 6

Special Populations and Situations

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours is optimal, providing single-agent coverage for both streptococci and MRSA 1
• Levofloxacin 500 mg daily for 5 days is an alternative (reserve fluoroquinolones for beta-lactam allergies) 1

Bite-Associated Cellulitis

• Amoxicillin-clavulanate 875/125 mg twice daily as monotherapy provides single-agent coverage for polymicrobial oral flora 1
• Do NOT add SMX-TMP to this regimen (SMX-TMP has poor anaerobic activity) 1

Diabetic Foot Infections

• Consider beta-lactam/beta-lactamase inhibitor combinations (amoxicillin-clavulanate) or second/third-generation cephalosporins (cefuroxime, ceftriaxone) for broader coverage 1