What is the recommended treatment for an adult patient with cellulitis, considering potential penicillin allergy and local resistance patterns?

Treatment for Cellulitis

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage is unnecessary in most cases. 1

Recommended Oral Agents for Uncomplicated Cellulitis

• Cephalexin 500 mg orally four times daily is the preferred first-line agent for typical nonpurulent cellulitis 1, 2
• Alternative beta-lactam options include dicloxacillin 250-500 mg every 6 hours, amoxicillin, or penicillin V 250-500 mg four times daily 1, 2
• Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily is specifically appropriate for bite-associated cellulitis (human or animal) 1

Treatment Duration

• Treat for exactly 5 days if clinical improvement has occurred 1, 2
• Extend treatment beyond 5 days ONLY if symptoms have not improved within this initial timeframe 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Evidence of MRSA infection elsewhere or known MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) 1

MRSA-Active Regimens

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, avoiding the need for combination therapy 1, 3
• Use clindamycin ONLY if local MRSA resistance rates are <10% 1
• Alternative combination regimens: trimethoprim-sulfamethoxazole (1-2 double-strength tablets twice daily) PLUS a beta-lactam, or doxycycline (100 mg twice daily) 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, 4

Management of Penicillin Allergy

For Patients with Penicillin Allergy

• Cephalexin 500 mg four times daily can be used in most penicillin-allergic patients, as cross-reactivity is less common than historically believed 1
• Clindamycin 300-450 mg every 6 hours is the optimal choice for patients with true penicillin allergy, providing coverage for both streptococci and MRSA 1, 3
• Fluoroquinolones (levofloxacin 500 mg daily or moxifloxacin 400 mg daily) can be reserved for patients with beta-lactam allergies, though they lack reliable MRSA coverage 1, 3

For Patients with Both Penicillin AND Sulfonamide Allergy

• Clindamycin 300-450 mg orally every 6 hours for 5 days is the definitive choice, providing single-agent coverage without requiring combination therapy 1, 3

Intravenous Therapy for Severe or Complicated Cellulitis

Standard IV Therapy for Hospitalized Patients

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis requiring hospitalization (A-I evidence) 1, 3
• Equally effective alternatives 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 every 8 hours if local resistance <10% 1, 3
• For uncomplicated cellulitis requiring hospitalization without MRSA risk factors, cefazolin 1-2 g IV every 8 hours remains appropriate 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 g IV every 6 hours 1
• Alternative combinations: linezolid PLUS piperacillin-tazobactam, or vancomycin PLUS a carbapenem 1
• Treatment duration for severe infections is 7-10 days, with reassessment at 5 days 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, 3
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, and treat these conditions to reduce recurrence risk 1, 2
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 2

Indications for Hospitalization

Hospitalize patients with any of the following:

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for deeper or necrotizing infection 1, 2
• Failure of outpatient treatment 2

Prevention of Recurrent Cellulitis

• For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics 1, 2
• Options include oral penicillin V 250 mg twice daily, oral erythromycin 250 mg twice daily, or intramuscular benzathine penicillin G monthly 1, 2, 5
• Monthly intramuscular clindamycin 300-600 mg can serve as a reasonable alternative to benzathine penicillin G, reducing recurrence risk by 77% 5

Critical Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance 1
• Do not extend treatment to 7-10 days based on tradition if clinical improvement has occurred by day 5 1, 2
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as streptococcal coverage will be inadequate 1
• Do not delay surgical consultation if any signs of necrotizing infection are present (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1