What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy (such as cephalexin, dicloxacillin, or amoxicillin) for 5 days is the standard of care, as MRSA coverage is unnecessary in most cases and provides no additional benefit. 1

Initial Antibiotic Selection

Standard Uncomplicated Cellulitis (No Purulence or MRSA Risk Factors)

Beta-lactam monotherapy is successful in 96% of patients and should be the default choice. 1 The pathogen is typically beta-hemolytic streptococci, not MRSA. 2, 3

Recommended oral agents include: 2, 1

• Cephalexin
• Dicloxacillin
• Amoxicillin
• Amoxicillin-clavulanate (Augmentin)
• Penicillin
• Clindamycin (covers both streptococci and MRSA as monotherapy)

Treatment duration is 5 days if clinical improvement occurs, with extension only if symptoms have not improved. 2, 1 Traditional 7-14 day courses are no longer necessary. 1

When to Add MRSA Coverage

MRSA coverage is indicated only when specific risk factors are present: 2, 1

• Penetrating trauma
• Purulent drainage present
• Evidence of MRSA infection elsewhere or known nasal colonization
• Injection drug use
• Systemic inflammatory response syndrome (SIRS)
• Athletes, prisoners, military recruits, long-term care residents 3

For these cases requiring MRSA coverage, use combination therapy: 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) plus a beta-lactam (e.g., cephalexin), OR
• Doxycycline 100 mg twice daily plus a beta-lactam 1
• Clindamycin monotherapy is an alternative that covers both streptococci and MRSA without requiring true combination therapy 1

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical nonpurulent cellulitis, as these agents lack reliable activity against beta-hemolytic streptococci. 1 A randomized controlled trial confirmed that adding TMP-SMX to cephalexin provides no benefit in pure cellulitis without abscess or purulent drainage. 4

Severe Infections Requiring Hospitalization

Hospitalize patients with: 2, 1

• SIRS, altered mental status, or hemodynamic instability
• Concern for necrotizing infection or rapid progression
• Severe immunocompromise
• Poor adherence anticipated

For severe infections, use broad-spectrum IV combination therapy: 2, 1

• Vancomycin or linezolid PLUS piperacillin-tazobactam, OR
• Vancomycin or linezolid PLUS a carbapenem (imipenem/meropenem), OR
• Vancomycin or linezolid PLUS ceftriaxone and metronidazole

For documented group A streptococcal necrotizing fasciitis specifically, use penicillin plus clindamycin. 1

Special Circumstances

For cellulitis associated with human or animal bites: Amoxicillin-clavulanate 875/125 mg twice daily provides single-agent coverage for both streptococci and common oral flora. 1

For pediatric patients over 8 years requiring MRSA coverage: Doxycycline 2 mg/kg/dose orally every 12 hours (maximum 100 mg/dose) combined with a beta-lactam. 1 Never use doxycycline in children under 8 years due to tooth discoloration and bone growth effects. 1

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting drainage. 2, 1

Examine interdigital toe spaces in lower extremity cellulitis and treat any fissuring, scaling, or maceration, as this eradicates pathogen colonization and reduces recurrence risk. 2, 1

Address predisposing conditions: 2, 1

• Edema and venous insufficiency
• Obesity
• Eczema or other cutaneous disorders
• Tinea pedis (athlete's foot)

Diagnostic Testing

Cultures of blood or cutaneous specimens are NOT routinely recommended for typical cellulitis. 2 Only 15% of cases yield positive cultures, and most are due to beta-hemolytic streptococci and methicillin-sensitive S. aureus. 3

Blood cultures and tissue sampling should be obtained only in: 2

• Malignancy with chemotherapy
• Neutropenia
• Severe cell-mediated immunodeficiency
• Immersion injuries
• Animal bites

Common Pitfalls

Do not reflexively add MRSA coverage based on local community prevalence alone—beta-lactam monotherapy remains highly effective for typical cellulitis even in MRSA-prevalent areas. 1, 4 The randomized trial by Pallin et al. definitively showed no benefit from adding TMP-SMX to cephalexin in uncomplicated cellulitis. 4

Do not continue antibiotics beyond 5 days if clinical improvement has occurred—this is unnecessary and contributes to antibiotic resistance. 2, 1

Failure to improve on appropriate first-line antibiotics should prompt consideration for: 3

• Resistant organisms
• Conditions that mimic cellulitis (venous stasis, contact dermatitis)
• Underlying complications (immunosuppression, chronic liver/kidney disease)
• Deeper or necrotizing infection