What are the best antibiotics (abx) for skin and cellulitis?

Best Antibiotics for Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy with cephalexin, dicloxacillin, penicillin, or amoxicillin is the standard of care and is successful in 96% of patients—MRSA coverage is unnecessary in most cases. 1, 2

First-Line Oral Antibiotic Options

Beta-lactam monotherapy is recommended for typical non-purulent cellulitis:

• Cephalexin 500 mg four times daily 1, 2, 3
• Dicloxacillin (standard dosing per FDA label) 1
• Penicillin 1, 2
• Amoxicillin 1, 2
• Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily, particularly appropriate for bite-associated cellulitis 1, 2
• Clindamycin as monotherapy provides coverage for both streptococci and MRSA, making it useful when dual coverage is desired without combination therapy 1, 2

Treatment Duration

Treat for 5 days if clinical improvement has occurred—extending beyond 5 days is only necessary if symptoms have not improved. 1, 2, 3

• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1, 2
• The 2019 NICE guideline recommends 5-7 days based on systematic reviews showing no benefit to longer courses 1

When to Add MRSA Coverage

MRSA is an uncommon cause of typical cellulitis and routine coverage is not recommended. 1, 2, 3

Add MRSA coverage only in these specific situations:

• Penetrating trauma, especially injection drug use 1, 2, 3
• Purulent drainage present 1, 2
• Evidence of MRSA infection elsewhere or known nasal colonization 1, 3
• Systemic inflammatory response syndrome (SIRS) with fever, hypotension, or altered mental status 1, 3

When MRSA coverage is needed, options include:

Oral Regimens:

• Clindamycin alone (covers both streptococci and MRSA) 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) plus a beta-lactam (cephalexin, penicillin, or amoxicillin) 1, 2
• Doxycycline plus a beta-lactam 1, 2

Intravenous Options (for severe infections):

• Vancomycin 1
• Daptomycin 1
• Linezolid 1

Critical Evidence Point

Adding TMP-SMX to cephalexin provides no additional benefit in pure cellulitis without abscess, ulcer, or purulent drainage. 1, 2, 4

• A randomized controlled trial demonstrated that combination therapy with TMP-SMX plus cephalexin was no more efficacious than cephalexin alone (85% vs 82% cure rate, p=0.66) 4
• This confirms that beta-lactam monotherapy is sufficient for typical cellulitis 1, 2

Severe Infections Requiring Hospitalization

Broad-spectrum combination therapy is mandatory for:

• Signs of systemic toxicity or rapid progression 2, 3
• Suspected necrotizing fasciitis 2
• Hemodynamic instability or altered mental status 3
• Severe immunocompromise 3

Recommended IV combination regimens:

• Vancomycin or linezolid plus piperacillin-tazobactam 2
• Vancomycin or linezolid plus a carbapenem 2
• Vancomycin or linezolid plus ceftriaxone and metronidazole 2
• For documented group A streptococcal necrotizing fasciitis: penicillin plus clindamycin 2

Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2, 3

Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adult patients to reduce inflammation. 1, 3

Treat predisposing conditions including:

• Tinea pedis and other toe web abnormalities 1, 2
• Venous insufficiency and lymphedema 1, 2
• Obesity and eczema 1, 2

Common Pitfalls to Avoid

Do not routinely add MRSA coverage for typical non-purulent cellulitis—beta-lactam treatment is successful in 96% of patients, and adding MRSA coverage provides no additional benefit. 1, 2, 3

Do not extend treatment unnecessarily beyond 5 days if clinical improvement has occurred—this increases antibiotic exposure without improving outcomes. 1, 2, 3

Do not obtain blood cultures or tissue aspirates for typical cases—these are only indicated for patients with malignancy, severe systemic features (high fever, hypotension), or unusual predisposing factors (immersion injury, animal bites, neutropenia, severe immunodeficiency). 1

Do not rely on oral antibiotics for patients with severe illness, nausea, vomiting, or signs of systemic toxicity—these patients require IV therapy and often hospitalization. 3, 5