What is the recommended treatment for cellulitis?

Treatment of 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

Recommended Oral Agents

• Penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin are all appropriate first-line options for uncomplicated cellulitis 1, 2
• These agents provide adequate coverage against β-hemolytic streptococci and methicillin-sensitive S. aureus, which account for the majority of identified pathogens in cellulitis 3, 4

Treatment Duration

• Treat for 5 days if clinical improvement has occurred, extending only if symptoms have not improved within this timeframe 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• This shortened duration is as effective as 10-day courses when clinical improvement is demonstrated by day 5 2

When to Add MRSA Coverage

MRSA is an uncommon cause of typical cellulitis, and empiric coverage should be reserved for specific high-risk scenarios. 1, 2

Indications for MRSA-Active Therapy

Add MRSA coverage when cellulitis is associated with:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Known MRSA colonization or concurrent MRSA infection elsewhere 1
• Failure to respond to beta-lactam therapy after 48 hours 1

MRSA-Active Regimens

For outpatient treatment requiring MRSA coverage:

• Clindamycin monotherapy (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1

Critical caveat: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as they lack reliable activity against β-hemolytic streptococci 1

Severe Infections Requiring Hospitalization

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

Indications for IV Therapy and Hospitalization

• Systemic inflammatory response syndrome (SIRS), altered mental status, or hemodynamic instability 2, 5
• Severe pain out of proportion to examination findings (suggests necrotizing infection) 1
• Rapid progression, skin anesthesia, bullous changes, or gas in tissue 1
• Failure of outpatient treatment 2
• Severely immunocompromised patients 2

Recommended IV Regimens

First-line IV therapy for complicated cellulitis:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line agent with A-I level evidence) 1
• Alternative agents include linezolid 600 mg IV twice daily (A-I evidence), daptomycin 4 mg/kg IV once daily (A-I evidence), or clindamycin 600 mg IV three times daily (A-III evidence) 1

For severe infections with systemic toxicity or suspected necrotizing fasciitis:

• Vancomycin or linezolid PLUS piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours 1
• Alternative combinations include vancomycin plus a carbapenem or ceftriaxone plus metronidazole 1
• Duration: 7-14 days for severe infections, guided by clinical response 1

Special Consideration for Necrotizing Fasciitis

• Penicillin plus clindamycin is the specific recommended combination for documented group A streptococcal necrotizing fasciitis 1
• Emergent surgical consultation is mandatory if necrotizing infection is suspected 1

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting drainage of edema and inflammatory substances. 1, 2

Additional supportive measures:

• Treat predisposing conditions including tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, and obesity 1, 2
• Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1, 2

Transition to Oral Therapy

Patients can transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 1

• Appropriate oral options include cephalexin, dicloxacillin, or clindamycin 1
• For continued MRSA coverage, use clindamycin alone or TMP-SMX/doxycycline plus a beta-lactam 1

Prevention of Recurrent Cellulitis

Identify and treat predisposing conditions at the time of initial diagnosis to minimize recurrence risk. 2, 6

• Address edema, venous insufficiency, lymphedema, and toe web abnormalities 1, 2
• Examine interdigital toe spaces for tinea pedis and treat appropriately 1
• For patients with 3-4 episodes per year despite treatment of predisposing factors, consider prophylactic antibiotics 2

Common Pitfalls to Avoid

• Do not add MRSA coverage reflexively simply because the patient is hospitalized or because of high local MRSA prevalence—beta-lactam monotherapy succeeds in 96% of typical cases 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection 1
• Do not delay surgical consultation if any signs of necrotizing infection are present, as these progress rapidly 1
• Assess for abscess with ultrasound if there is clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics 1
• Mandatory reassessment in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1