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 Selection

For typical uncomplicated cellulitis, beta-lactam monotherapy is the standard of care and is successful in 96% of patients—MRSA coverage is unnecessary in most cases. 1

Recommended Oral Agents for Uncomplicated Cellulitis

• Cephalexin 500 mg four times daily is a preferred first-line option for outpatient treatment 1, 2
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and MSSA coverage 1
• Amoxicillin or amoxicillin-clavulanate are appropriate alternatives 1, 2
• Penicillin V 250-500 mg four times daily is effective for streptococcal coverage 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred—extend only if symptoms have not improved within this timeframe. 1, 2 This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases 1.

When to Add MRSA Coverage

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

• 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

When MRSA coverage is indicated:

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA (use only if local resistance <10%) 1, 2
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline alone is inadequate due to unreliable streptococcal coverage) 1, 3
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam 1

Management for Penicillin Allergy

For patients with penicillin allergy:

• Cephalexin 500 mg four times daily can be used in most penicillin-allergic patients (cross-reactivity is less common than historically believed) 1
• Clindamycin 300-450 mg every 6 hours is ideal for patients with true penicillin allergy, providing coverage for both streptococci and MRSA 1, 2
• Fluoroquinolones (levofloxacin 500 mg daily) should be reserved for patients with beta-lactam allergies, but lack adequate MRSA coverage 1

Inpatient Management and IV Antibiotics

Indications for Hospitalization

Admit patients with 1, 4:

• SIRS (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm)
• Hypotension or hemodynamic instability
• Altered mental status or confusion
• Severe immunocompromise or neutropenia
• Concern for necrotizing infection
• Failure of outpatient treatment

IV Antibiotic Selection

For hospitalized patients with uncomplicated cellulitis requiring IV therapy:

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1
• Oxacillin 2 g IV every 6 hours or nafcillin 2 g IV every 6 hours are alternatives 1

For complicated cellulitis requiring MRSA coverage:

• Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
• Linezolid 600 mg IV twice daily is equally effective (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily is an alternative (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 1:

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Duration: 7-10 days minimum, reassessing at 5 days 1

Essential Adjunctive Measures

Elevation of the affected extremity is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances 1, 2.

Additional measures include 1, 2, 4:

• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat if present
• Address venous insufficiency and lymphedema with compression stockings once acute infection resolves
• Treat eczema and other predisposing skin conditions
• Optimize glycemic control in diabetic patients

Special Populations

Diabetic Patients

For diabetic foot infections 4:

• Mild to moderate infections: oral agents covering streptococci and MSSA (amoxicillin-clavulanate, cephalexin)
• Severe infections: parenteral broad-spectrum therapy covering gram-positives, gram-negatives, and anaerobes
• Duration: 7-10 days for mild infections, up to 14-28 days for severe infections

Older Adults

• Use the same first-line agents (cephalexin, amoxicillin, dicloxacillin) 2
• Elevation is particularly important due to venous insufficiency 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic older adults to reduce inflammation 2

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors 1, 2:

• Oral penicillin V 250 mg twice daily for 4-52 weeks 1
• Oral erythromycin 250 mg twice daily for 4-52 weeks 1
• Intramuscular benzathine penicillin G 1.2-2.4 million units every 2-4 weeks 1, 5
• Intramuscular clindamycin 300-600 mg monthly may serve as a reasonable alternative to benzathine penicillin G 5

Critical Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis—MRSA is uncommon even in high-prevalence settings 1
• Do not extend treatment beyond 5 days based on residual erythema alone if clinical improvement has occurred 1, 2
• Do not use doxycycline as monotherapy—it lacks reliable streptococcal coverage and must be combined with a beta-lactam 1, 3
• Do not miss necrotizing fasciitis warning signs: severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, or bullous changes require emergent surgical consultation 1
• Do not forget to examine toe webs in lower extremity cellulitis—treating tinea pedis reduces recurrence 1, 2