What is the initial treatment for a patient presenting with cellulitis?

Initial Treatment for Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy is the standard of care and succeeds in 96% of patients—MRSA coverage is NOT needed unless specific risk factors are present. 1

First-Line Antibiotic Selection

Outpatient Oral Therapy (Nonpurulent Cellulitis)

Choose any of these beta-lactam options for typical cases 1:

• Cephalexin 500 mg orally four times daily 1
• Dicloxacillin 250-500 mg orally every 6 hours 1
• Amoxicillin-clavulanate (Augmentin) 875/125 mg orally twice daily 1
• Penicillin or amoxicillin (alternative options) 1
• Clindamycin 300-450 mg orally three times daily (covers both streptococci and MRSA if local resistance <10%) 1

Inpatient IV Therapy (Uncomplicated Cellulitis Requiring Hospitalization)

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1
• Oxacillin or nafcillin are alternatives 1
• Beta-lactam monotherapy remains appropriate even in the hospital setting if the cellulitis is nonpurulent and lacks MRSA risk factors 1

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend ONLY if symptoms have not improved within this timeframe. 1 Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1.

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when these specific risk factors are present 1:

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

MRSA-Active Regimens (When Indicated)

For outpatient purulent cellulitis requiring MRSA coverage 1:

• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
• Clindamycin 300-450 mg orally three times daily as monotherapy (covers both streptococci and MRSA) 1

Critical caveat: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci, the primary pathogen 1.

Severe Cellulitis Requiring Broad-Spectrum Coverage

For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use 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 1, 2
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem or ceftriaxone plus metronidazole 1

Duration for severe infections: 7-14 days, guided by clinical response 1.

Hospitalization Criteria

Admit patients with any of the following 1:

• SIRS (fever, tachycardia, tachypnea, leukocytosis) 1
• Hemodynamic instability or altered mental status 1
• Severe immunocompromise or neutropenia 1
• Suspected necrotizing infection (severe pain out of proportion, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1

Adjunctive Measures

• Elevate the affected extremity to promote drainage and hasten improvement 1
• Examine interdigital toe spaces for tinea pedis and treat toe web abnormalities to reduce recurrence risk 1
• Address predisposing conditions including edema, venous insufficiency, lymphedema, and obesity 1
• Consider systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Common Pitfalls to Avoid

• Do NOT reflexively add MRSA coverage simply because the patient is hospitalized or because MRSA prevalence is high in your area—MRSA is an uncommon cause of typical nonpurulent cellulitis even in high-prevalence settings 1
• Do NOT continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection 1
• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics 1
• Obtain emergent surgical consultation if any signs of necrotizing infection are present—these progress rapidly and require debridement 1

Transition to Oral Therapy (Inpatient Setting)

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

• Cephalexin, dicloxacillin, or clindamycin for continued therapy 1
• If MRSA coverage is needed, use clindamycin alone or TMP-SMX/doxycycline plus a beta-lactam 1