What is the recommended treatment for a cellulitis (bacterial skin infection) inpatient?

Treatment of Cellulitis in Hospitalized Patients

First-Line Antibiotic Selection

For typical uncomplicated cellulitis requiring hospitalization, IV cefazolin (1-2 g every 8 hours) or oxacillin is the standard of care, as beta-lactam monotherapy succeeds in 96% of cases and MRSA coverage is unnecessary in most hospitalized patients. 1

When Beta-Lactam Monotherapy is Appropriate:

• Non-purulent cellulitis without drainage or exudate 1
• Absence of penetrating trauma or injection drug use 1
• No evidence of MRSA colonization elsewhere 1
• No systemic inflammatory response syndrome (SIRS) 1

The Infectious Diseases Society of America emphasizes that MRSA is an uncommon cause of typical cellulitis even in hospitals with high MRSA prevalence, and reflexive addition of MRSA coverage simply because a patient is hospitalized is not warranted 1.

When to Add MRSA Coverage

Add vancomycin (15-20 mg/kg IV every 8-12 hours) or linezolid (600 mg IV twice daily) ONLY when specific risk factors are present: 1

• Purulent drainage or exudate 1
• Penetrating trauma or injection drug use 1
• Known MRSA colonization 1
• Systemic toxicity (fever, hypotension, altered mental status) 1
• Failure to respond to beta-lactam therapy after 48 hours 1

Both vancomycin and linezolid have A-I level evidence supporting their use, with cure rates of 79% and 90% respectively in complicated skin infections 2.

Severe Cellulitis Requiring Broad-Spectrum Coverage

For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy includes vancomycin or linezolid PLUS piperacillin-tazobactam (3.375-4.5 g IV every 6 hours), a carbapenem, or ceftriaxone plus metronidazole. 1

Warning Signs Requiring Escalation:

• Severe pain out of proportion to examination 1
• Skin anesthesia or bullous changes 1
• Gas in tissue 1
• Rapid progression despite appropriate antibiotics 1
• Hemodynamic instability 1

If necrotizing infection is suspected, obtain emergent surgical consultation immediately—these infections progress rapidly and require debridement 1.

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 3

• For uncomplicated cellulitis: 5 days 1
• For severe infections with systemic toxicity: 7-10 days, reassessing at 5 days 1
• For necrotizing fasciitis or infections requiring surgical debridement: 7-14 days 1

Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1. The duration may be influenced by patient age, C-reactive protein levels, diabetes mellitus, and presence of bacteremia 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 combination therapy with trimethoprim-sulfamethoxazole or doxycycline plus a beta-lactam 1. Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1.

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 3

Additional measures include:

• Treating predisposing conditions (tinea pedis, venous insufficiency, lymphedema, eczema) 1, 3
• Examining and treating toe web abnormalities 1
• Considering systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Critical Pitfalls to Avoid

• Do not add MRSA coverage reflexively simply because the patient is hospitalized—beta-lactam monotherapy is successful in 96% of typical cases 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection 1
• Do not delay surgical consultation if any signs of necrotizing infection are present 1
• Do not obtain blood cultures routinely unless the patient has malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1
• Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1