What is the treatment for cellulitis of the leg?

Treatment of Leg Cellulitis

For typical uncomplicated leg cellulitis, treat with beta-lactam monotherapy (such as cephalexin 500 mg four times daily, dicloxacillin 250-500 mg every 6 hours, or amoxicillin) for 5 days if clinical improvement occurs—MRSA coverage is NOT needed unless specific risk factors are present. 1, 2

First-Line Antibiotic Selection

Beta-lactam monotherapy is the standard of care and succeeds in 96% of cases because typical leg cellulitis is caused by beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, not MRSA. 1, 2, 3

Oral Options for Outpatient Treatment:

• Cephalexin 500 mg four times daily 2, 4
• Dicloxacillin 250-500 mg every 6 hours 2, 4
• Amoxicillin (standard dosing) 1, 2
• Penicillin V 250-500 mg four times daily 1, 4
• Clindamycin 300-450 mg three times daily (covers both streptococci and MRSA, useful for penicillin-allergic patients) 2, 4

Intravenous Options for Hospitalized Patients:

• Cefazolin 1-2 g IV every 8 hours (preferred IV beta-lactam) 1, 2
• Nafcillin 2 g IV every 6 hours 1
• 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, 5 This represents a major shift from traditional 7-14 day courses, supported by high-quality randomized controlled trial evidence showing 5 days of levofloxacin was equally effective as 10 days (98% success rate in both groups). 5

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical nonpurulent leg cellulitis. 1, 2 MRSA is an uncommon cause even in high-prevalence settings. 2, 3

Add MRSA-Active Antibiotics ONLY When These Specific Risk Factors Are Present:

• Penetrating trauma or injection drug use 1, 2, 4
• Purulent drainage or exudate 1, 2, 4
• Evidence of MRSA infection elsewhere or known MRSA colonization 2, 4
• Systemic inflammatory response syndrome (SIRS) with fever >38.5°C, heart rate >110 bpm, or WBC >12,000/µL 1, 2
• Athletes, prisoners, military recruits, or residents of long-term care facilities 3

MRSA-Active Regimens When Indicated:

• Clindamycin monotherapy 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 2, 4
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (never use TMP-SMX alone due to poor streptococcal coverage) 2, 6
• Doxycycline 100 mg twice daily PLUS a beta-lactam (never use doxycycline alone) 2

In a high MRSA-prevalence setting, trimethoprim-sulfamethoxazole achieved 91% treatment success versus 74% for cephalexin alone, demonstrating superiority when MRSA is present. 6

Severe Cellulitis Requiring Hospitalization

Indications for Hospitalization:

• Systemic toxicity (fever, hypotension, tachycardia, altered mental status) 1, 2, 4
• Rapid progression or concern for necrotizing fasciitis 1, 2
• Severe immunocompromise or neutropenia 2, 4
• Hemodynamic instability 2, 4

Broad-Spectrum IV Combination Therapy for Severe Infections:

Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours is the recommended empiric regimen for severe cellulitis with systemic signs. 1, 2

Alternative combinations include:

• Vancomycin or linezolid PLUS a carbapenem 1, 2
• Vancomycin or linezolid PLUS ceftriaxone and metronidazole 1, 2

For severe infections, treat for 7-14 days guided by clinical response. 2

Essential Adjunctive Measures

Elevation of the affected leg is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2

Address Predisposing Factors:

• Treat tinea pedis and interdigital toe web abnormalities (examine carefully between toes) 1, 4
• Manage venous insufficiency with compression stockings 1
• Treat venous eczema ("stasis dermatitis") 1
• Reduce lymphedema with elevation, compression, or diuretics if appropriate 1
• Keep skin well-hydrated with emollients to prevent cracking 1

Optional Corticosteroid Therapy:

Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in nondiabetic adult patients to attenuate inflammatory reactions and hasten resolution, though evidence is limited (weak recommendation, moderate evidence). 1 One randomized trial showed median healing time shortened by 1 day with prednisolone. 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:

• Oral penicillin V 1 g twice daily for 4-52 weeks 1
• Oral erythromycin 250 mg twice daily for 4-52 weeks 1
• Intramuscular benzathine penicillin 1.2 million units every 2-4 weeks 1, 4

Continue prophylaxis as long as predisposing factors persist. 1

Critical Pitfalls to Avoid

• Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis—their activity against beta-hemolytic streptococci is unreliable. 2
• Do not reflexively add MRSA coverage simply because the patient is hospitalized—beta-lactam monotherapy remains appropriate for uncomplicated cellulitis even in the inpatient setting. 2
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection requiring reassessment. 2
• Reassess within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens. 2
• Evaluate for necrotizing fasciitis if severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, or bullous changes are present—these require emergent surgical consultation. 2