What are the recommended antibiotics for post-operative cellulitis?

Recommended Antibiotics for Post-Operative Cellulitis

First-Line Treatment Selection

For post-operative cellulitis of the trunk or extremities, cefazolin 0.5-1 g IV every 8 hours or cephalexin 500 mg PO every 6 hours is the first-line treatment, targeting Staphylococcus aureus and Streptococcus species. 1

The choice between IV and oral therapy depends on severity and ability to tolerate oral medications:

• Inpatient/IV therapy: Cefazolin 0.5-1 g IV every 8 hours is preferred 1, 2
• Outpatient/oral therapy: Cephalexin 500 mg PO every 6 hours 1
• Alternative IV options: Oxacillin or nafcillin 2 g IV every 6 hours 1

Site-Specific Antibiotic Selection

The surgical site determines appropriate coverage:

Trunk or Extremity Surgery

• First-line: Cefazolin or cephalexin (as above) 1
• Beta-lactam monotherapy is successful in 96% of typical cases 3

Axilla or Perineum Surgery

• Combination therapy required: Metronidazole 500 mg IV every 8 hours PLUS either:
  • Ciprofloxacin 400 mg IV every 12 hours (or 750 mg PO every 12 hours), OR
  • Ceftriaxone 1 g IV every 24 hours 1, 4

Intestinal or Genitourinary Tract Surgery

• Single-drug option: Piperacillin-tazobactam 3.375 g IV every 6 hours or 4.5 g every 8 hours 1
• Once-daily alternative: Ertapenem 1 g IV every 24 hours 1

When to Add MRSA Coverage

Do not routinely add MRSA coverage for typical post-operative cellulitis, as MRSA is an unusual cause of standard cellulitis. 1, 3

Add vancomycin 15 mg/kg IV every 12 hours ONLY if these specific risk factors are present: 1, 3

• Penetrating trauma
• Evidence of MRSA infection elsewhere
• Known MRSA nasal colonization
• Purulent drainage or exudate
• Failure to respond to beta-lactam therapy after 48 hours

Treatment Duration

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

This shortened duration is supported by high-quality evidence:

• A randomized controlled trial demonstrated 98% success rates with 5 days versus 10 days of levofloxacin for uncomplicated cellulitis 5
• The 5-day duration applies regardless of whether IV or oral antibiotics are used 3, 1

For complicated infections requiring broad-spectrum coverage or those with systemic toxicity, plan for 7-14 days guided by clinical response 3

Inpatient vs. Outpatient Decision Algorithm

Hospitalize if any of the following are present: 1

• Systemic inflammatory response syndrome (SIRS)
• Altered mental status
• Hemodynamic instability
• Signs of systemic toxicity (fever, hypotension, tachycardia, confusion)

Outpatient oral therapy is appropriate for: 1

• Most post-operative cellulitis cases without systemic signs
• Patients who can self-monitor with close follow-up
• Stable vital signs and no evidence of deep infection

Adjunctive Measures

Beyond antibiotics, these interventions hasten resolution: 1, 3

• Elevation of the affected area to promote drainage of edema and inflammatory substances
• Remove sutures if purulent collection is present and perform incision and drainage
• Systemic corticosteroids: Consider prednisone 40 mg daily for 7 days in non-diabetic adults (weak recommendation, moderate evidence)

Penicillin-Allergic Patients

Alternative regimens for true penicillin allergy: 1

• Clindamycin (dose varies by severity)
• Trimethoprim-sulfamethoxazole 160-800 mg PO every 6 hours

Critical caveat: Doxycycline or trimethoprim-sulfamethoxazole should NOT be used as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 3

Severe Infections Requiring Broad Coverage

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis: 3, 1

• Vancomycin 15 mg/kg IV every 12 hours PLUS piperacillin-tazobactam 4.5 g IV every 8 hours, OR
• Vancomycin PLUS a carbapenem

Obtain emergent surgical consultation if necrotizing infection is suspected, as these require debridement in addition to antibiotics 3

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is post-operative or hospitalized—beta-lactam monotherapy succeeds in 96% of typical cases 3, 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection requiring reassessment 3
• Mandatory reassessment in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 3
• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics 3