What are the best IV medications for treating cellulitis?

Best IV Medications for Cellulitis

For typical uncomplicated cellulitis requiring hospitalization, cefazolin 1-2 grams IV every 8 hours is the preferred first-line agent, with a 96% success rate in beta-lactam monotherapy. 1

Standard IV Therapy for Uncomplicated Cellulitis

Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis or when MRSA coverage is needed (A-I evidence). 1 However, MRSA coverage should NOT be added reflexively just because a patient is hospitalized—MRSA remains an uncommon cause of typical cellulitis even in high-prevalence settings. 1

Preferred IV Beta-Lactams (Non-MRSA Coverage)

• Cefazolin 1-2 grams IV every 8 hours is the preferred IV beta-lactam for hospitalized patients with uncomplicated cellulitis without MRSA risk factors. 1
• Oxacillin 2 grams IV every 6 hours is an alternative. 1
• Nafcillin 2 grams IV every 6 hours is another alternative. 1

MRSA-Active IV Agents (When Risk Factors Present)

Add MRSA coverage ONLY when specific risk factors exist: purulent drainage, penetrating trauma, injection drug use, known MRSA colonization, or systemic inflammatory response syndrome. 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours (A-I evidence) 1
• Linezolid 600 mg IV twice daily (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV every 8 hours (A-III evidence)—only if local MRSA clindamycin resistance is <10% 1, 2
• Telavancin 10 mg/kg IV once daily (A-I evidence) 1

Severe Cellulitis with Systemic Toxicity

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 grams IV every 6 hours. 1

Alternative Severe Infection Combinations

• Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Vancomycin PLUS a carbapenem (meropenem 1 gram IV every 8 hours) 1
• Vancomycin PLUS ceftriaxone 2 grams IV daily and metronidazole 500 mg IV every 8 hours 1

Indications for Broad-Spectrum Therapy

Hospitalize and use combination therapy if ANY of the following are present: 1

• Systemic inflammatory response syndrome (SIRS)
• Fever, hypotension, or altered mental status
• Severe immunocompromise or neutropenia
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes)

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 For severe cellulitis with systemic toxicity or necrotizing fasciitis, treatment should continue for 7-14 days guided by clinical response. 1

Pediatric IV Antibiotic Selection

• Vancomycin 15 mg/kg IV every 6 hours is first-line for hospitalized children with complicated cellulitis. 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours is an option if the child is stable without ongoing bacteremia and local clindamycin resistance is <10%. 1
• Linezolid 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years. 1

Critical Pitfalls to Avoid

Do NOT use piperacillin-tazobactam alone for cellulitis—it lacks MRSA activity and must always be combined with vancomycin or linezolid if used. 1 Piperacillin-tazobactam is indicated only for severe cellulitis with systemic toxicity or suspected polymicrobial/necrotizing infection. 1, 3

Do NOT add MRSA coverage reflexively for typical nonpurulent cellulitis simply because the patient is hospitalized. 1 Beta-lactam monotherapy succeeds in 96% of cases. 1, 4

Transition to Oral Therapy

Patients can transition to oral antibiotics (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 1 For continued MRSA coverage orally, use clindamycin alone or doxycycline/trimethoprim-sulfamethoxazole PLUS a beta-lactam. 1

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema. 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat to eradicate colonization. 1, 2
• Treat predisposing conditions including venous insufficiency, lymphedema, and chronic edema. 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited. 1