What are the recommended antibiotics for treating cellulitis?

Antibiotics for Cellulitis

First-Line Treatment

For uncomplicated nonpurulent cellulitis, use beta-lactam monotherapy (cephalexin 500 mg four times daily, penicillin, or amoxicillin) for 5-6 days, as this approach achieves 96% success rates and MRSA coverage is unnecessary in typical cases. 1, 2

Recommended Oral Agents for Standard Cellulitis

• Cephalexin 500 mg four times daily is the preferred first-line agent for most patients with uncomplicated cellulitis 2
• Penicillin or amoxicillin are equally effective alternatives 2
• Clindamycin 300-450 mg four times daily should be used for penicillin-allergic patients 2
• Treatment duration is 5-6 days if clinical improvement occurs, with extension only if symptoms have not improved after this initial period 3, 1, 2

The evidence strongly supports that beta-lactam monotherapy is successful in 96% of typical cellulitis cases, confirming that routine MRSA coverage is unnecessary 1. This is reinforced by a randomized controlled trial showing that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit over cephalexin alone 4.

When to Add MRSA Coverage

Add MRSA-active antibiotics only when specific risk factors are present, not routinely 3:

MRSA Risk Factors Requiring Combination Therapy

• Cellulitis associated with penetrating trauma 3, 2
• Evidence of MRSA infection elsewhere or nasal colonization 3, 2
• Injection drug use 3, 2
• Purulent drainage present 3, 2
• Systemic inflammatory response syndrome (SIRS) 3, 2

Combination Regimens When MRSA Coverage Needed

• Trimethoprim-sulfamethoxazole (TMP-SMX) plus cephalexin 1, 2
• Doxycycline 100 mg twice daily plus a beta-lactam 1
• Clindamycin monotherapy (covers both streptococci and MRSA, avoiding need for true combination therapy) 1, 2

Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical nonpurulent cellulitis, as tetracyclines and sulfonamides lack reliable activity against beta-hemolytic streptococci 1.

Severe Infections Requiring Hospitalization

Broad-spectrum IV combination therapy is mandatory for patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis 1, 2:

IV Combination Regimens for Severe Disease

• Vancomycin plus piperacillin-tazobactam for severely compromised patients with SIRS 2
• Vancomycin or linezolid plus a carbapenem (imipenem/meropenem) for suspected necrotizing fasciitis 1, 2
• Penicillin plus clindamycin specifically for documented group A streptococcal necrotizing fasciitis 1, 2

Hospitalization Criteria

• Systemic inflammatory response syndrome, altered mental status, or hemodynamic instability 2
• Concern for deeper or necrotizing infection 2
• Severe immunocompromise or failed outpatient therapy 2

Special Circumstances

Bite-Associated Cellulitis

Amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily is appropriate for cellulitis from human or animal bites, providing single-agent coverage for both streptococci and common oral flora 1

Route of Administration

Oral antibiotics are as effective as IV therapy for cellulitis of similar severity 5. Research demonstrates that patients receiving only oral therapy were more likely to have improved at day 5 compared to those given IV therapy, with equivalent outcomes at days 10 and 30 5. The oral route offers advantages of rapid first-dose delivery and simplified medication administration, particularly in children 6.

Adjunctive Measures

• Elevate the affected extremity to promote drainage and hasten improvement 1, 2
• Examine and treat interdigital toe spaces for tinea pedis, as this serves as a portal of entry 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 2
• Treat predisposing conditions including edema, obesity, eczema, venous insufficiency, and toe web abnormalities 1

Common Pitfalls to Avoid

• Do not routinely prescribe MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents unnecessary broad-spectrum antibiotic use 1, 2
• Do not extend treatment beyond 5-6 days unless clinical improvement has not occurred—traditional 7-14 day courses are no longer necessary 1, 2
• Do not use doxycycline in children under 8 years due to tooth discoloration and bone growth effects 1
• Do not use doxycycline in pregnant women (pregnancy category D) 1