What is the recommended treatment for cellulitis?

Recommended Treatment for Cellulitis

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, confirming that MRSA coverage is usually unnecessary. 1

Oral Antibiotic Options

• Cephalexin 500 mg every 6 hours is the preferred first-line agent for typical cellulitis, providing effective coverage against streptococci and methicillin-sensitive S. aureus 1, 2
• Alternative oral agents include penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin (250-500 mg every 6 hours), or clindamycin 1, 2
• All these agents target the primary pathogens: β-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive S. aureus, which account for the majority of culturable cases 3, 4

Intravenous Antibiotic Options

• Cefazolin 1-2 g IV every 8 hours is the preferred IV agent for hospitalized patients requiring parenteral therapy 1
• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis requiring MRSA coverage (A-I evidence) 1
• Alternative IV agents with equivalent efficacy include linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV once daily, or clindamycin 600 mg IV three times daily (if local MRSA resistance <10%) 1

Treatment Duration

Treat for 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2

• Five-day courses are as effective as 10-14 day courses for uncomplicated cellulitis 1, 2
• This represents a significant departure from traditional 7-14 day courses, which are no longer necessary 1
• Reassess within 24-48 hours for outpatients to ensure clinical improvement 1

When to Add MRSA Coverage

MRSA is an uncommon cause of typical cellulitis, and adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 1

Specific Indications for MRSA Coverage

Add MRSA-active antibiotics ONLY when these risk factors are present:

• Penetrating trauma or injection drug use 1, 2, 3
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1, 2
• Systemic inflammatory response syndrome (SIRS) criteria: fever, tachycardia, hypotension, altered mental status 1, 2
• Failure to respond to beta-lactam therapy after 48 hours 1

MRSA Coverage Options

When MRSA coverage is indicated:

• Clindamycin 300-450 mg orally three times daily provides single-agent coverage for both streptococci and MRSA (if local resistance <10%) 1, 5
• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (cephalexin, penicillin, or amoxicillin) 1, 5
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
• Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as they lack reliable activity against β-hemolytic streptococci 1

Severe Infections Requiring Broad-Spectrum Coverage

Broad-spectrum combination therapy is mandatory for patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis. 1

Warning Signs Requiring Immediate Escalation

• Severe pain out of proportion to examination 1
• Skin anesthesia, rapid progression, gas in tissue 1
• Bullous changes, systemic toxicity 1
• Hemodynamic instability, altered mental status 1, 2

Recommended 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
• For documented group A streptococcal necrotizing fasciitis: penicillin plus clindamycin 1

Hospitalization Criteria

Admit patients who have:

• SIRS criteria (fever, altered mental status, hemodynamic instability) 1, 2
• Concern for deeper or necrotizing infection 1, 2
• Poor adherence to outpatient therapy 2
• Severe immunocompromise or neutropenia 1, 2
• Failure of outpatient treatment after 24-48 hours 1, 2

Essential Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances 1, 2
• Examine interdigital toe spaces carefully for tinea pedis, fissuring, scaling, or maceration and treat if present 1, 2
• Treat predisposing conditions: venous insufficiency, lymphedema, eczema, obesity 1, 2
• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1, 2
• Avoid corticosteroids in diabetic patients 1

Special Considerations for Comorbidities

Diabetes Mellitus

• Patients with diabetes require longer treatment duration compared to non-diabetic patients, with median treatment extending beyond the standard 5-day course 1, 6
• Avoid systemic corticosteroids in diabetic patients despite evidence showing benefit in non-diabetics 1

Chronic Kidney Disease

• Avoid clindamycin as first-line due to nephrotoxicity concerns 1

Blood Stream Infection

• Duration of treatment is significantly longer in patients with coexisting blood stream infection 6

Prevention of Recurrence

For patients with 3-4 episodes per year despite treating predisposing factors:

• Consider prophylactic antibiotics: oral penicillin or erythromycin twice daily for 4-52 weeks 1
• Alternative: intramuscular benzathine penicillin every 2-4 weeks 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors—MRSA is an unusual cause and treatment is usually unnecessary 1, 2, 5
• Do not extend treatment beyond 5 days automatically; only extend if clinical improvement has not occurred 1
• Do not use doxycycline or TMP-SMX as monotherapy for typical nonpurulent cellulitis, as streptococcal coverage will be inadequate 1
• Blood cultures are positive in only 5% of cases and are unnecessary for typical cellulitis 1
• Obtain blood cultures only in patients with severe systemic features, malignancy, neutropenia, or unusual predisposing factors 1, 2
• If no improvement with appropriate first-line antibiotics after 48 hours, consider resistant organisms, cellulitis mimickers (venous stasis dermatitis, contact dermatitis), or underlying complications 1, 3