What is the treatment for leg cellulitis?

Treatment of Leg Cellulitis

For typical nonpurulent leg cellulitis, treat with beta-lactam monotherapy (cephalexin 500 mg four times daily, dicloxacillin 250-500 mg every 6 hours, or amoxicillin) for exactly 5 days if clinical improvement occurs—MRSA coverage is unnecessary in 96% of cases. 1

First-Line Antibiotic Selection

• Beta-lactam monotherapy is the standard of care for uncomplicated leg cellulitis, as β-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus cause the vast majority of cases 1, 2, 3
• Recommended oral agents include cephalexin 500 mg four times daily, dicloxacillin 250-500 mg every 6 hours, amoxicillin, or penicillin V 250-500 mg four times daily 1, 2
• For hospitalized patients requiring IV therapy, cefazolin 1-2 g IV every 8 hours is the preferred beta-lactam 1

Treatment Duration

• Treat for exactly 5 days if clinical improvement has occurred—this is based on high-quality randomized controlled trial evidence showing equivalence to longer courses 1, 2
• Extend treatment beyond 5 days 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 (and When NOT To)

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

Add MRSA-active antibiotics only when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use
• Purulent drainage or exudate from the wound
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, altered mental status

If MRSA coverage is needed, use: 1

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA as monotherapy, avoiding need for combination therapy)
• Alternatively: doxycycline 100 mg twice daily plus a beta-lactam (doxycycline alone is inadequate due to unreliable streptococcal coverage)
• Alternatively: trimethoprim-sulfamethoxazole plus a beta-lactam

Severe Cellulitis Requiring Hospitalization

Hospitalize if any of the following are present: 1, 4

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status
• Severe immunocompromise or neutropenia
• Severe pain out of proportion to examination findings (suggests necrotizing fasciitis)
• Rapid progression over hours rather than days

For severe cellulitis with systemic toxicity or suspected necrotizing fasciitis, use mandatory broad-spectrum combination therapy: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours
• Alternative combinations: linezolid 600 mg IV twice daily plus piperacillin-tazobactam, or vancomycin plus a carbapenem 1
• Obtain emergent surgical consultation if necrotizing infection is suspected 1

Essential Adjunctive Measures (Often Neglected)

• Elevate the affected leg above heart level for at least 30 minutes three times daily—this is critical and often overlooked, promoting gravity drainage of edema and inflammatory substances 5, 1, 2, 4
• Examine interdigital toe spaces daily for tinea pedis, fissuring, scaling, or maceration—this is the most common bacterial entry point 1, 2, 4
• Apply topical antifungal agents (clotrimazole, miconazole) to toe webs if any fungal infection is present 4
• Treat predisposing conditions including venous insufficiency, lymphedema, and chronic edema 5, 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to reduce inflammation, though evidence is limited 5, 1, 2

Prevention of Recurrent Cellulitis

• Annual recurrence rates are 8-20% after the first episode, rising substantially with repeated infections 4, 6
• Each episode causes permanent lymphatic damage, progressively worsening underlying lymphedema 4

For patients with 3-4 episodes per year despite optimal management of risk factors, strongly consider prophylactic antibiotics: 1, 2, 4

• Penicillin V 250 mg orally twice daily, continued indefinitely as long as risk factors persist 1, 2, 4
• Alternative: erythromycin 250 mg twice daily 5
• Prophylaxis reduces recurrence risk by 47% during treatment (HR 0.53,95% CI 0.26-1.07), with number needed to treat of 8 7, 8
• Critical caveat: protective effects diminish progressively once prophylaxis is stopped 6, 8

Use compression stockings (20-30 mmHg) during waking hours only after any active infection has completely resolved—never during acute cellulitis 4

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because local MRSA prevalence is high—beta-lactam monotherapy succeeds in 96% of typical cases 1, 2
• Do not use doxycycline as monotherapy for typical cellulitis—its activity against beta-hemolytic streptococci is unreliable 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection than initially recognized 1
• Do not delay surgical consultation if any signs of necrotizing infection are present (severe pain out of proportion, skin anesthesia, rapid progression, gas in tissue, bullous changes)—these infections progress rapidly and require debridement 1

Reassessment and Treatment Failure

• Mandatory reassessment in 24-48 hours to verify clinical response 1
• If spreading despite appropriate antibiotics, reassess for: 1
  • MRSA risk factors (switch to vancomycin or linezolid if present)
  • Necrotizing fasciitis (obtain emergent surgical consultation)
  • Misdiagnosis (consider conditions mimicking cellulitis)
  • Underlying complicating conditions (immunosuppression, chronic liver disease, chronic kidney disease) 3