What antibiotics are effective for treating cellulitis?

Antibiotic Treatment for Cellulitis

First-Line Therapy for Typical Cellulitis

For typical non-purulent cellulitis, start with a penicillinase-resistant penicillin (dicloxacillin) or first-generation cephalosporin (cephalexin) for 5-7 days, targeting beta-hemolytic streptococci, which are the primary causative organisms. 1

• Cephalexin 500 mg every 6 hours orally is the most commonly recommended first-line agent, providing effective coverage against Streptococcus pyogenes and methicillin-sensitive Staphylococcus aureus 1
• Dicloxacillin is equally effective as first-line therapy for uncomplicated cellulitis 1
• Amoxicillin is an appropriate alternative first-line option 2
• Penicillin alone can be used when streptococcal infection is strongly suspected 2

Treatment Duration

Five days of antibiotic therapy is as effective as 10 days for uncomplicated cellulitis if clinical improvement is evident. 1, 3

• Extend treatment beyond 5 days only if no clinical improvement is seen 2
• The IDSA recommends 5-10 days of therapy individualized based on clinical response 4

When MRSA Coverage is NOT Needed

MRSA is an unusual cause of typical cellulitis and routine coverage is unnecessary. 1

• Do not add MRSA coverage for non-purulent cellulitis without specific risk factors 1, 5
• A randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no benefit for non-purulent cellulitis 6

When to Add MRSA Coverage

Add empirical MRSA coverage only when specific high-risk features are present: 1

• Purulent drainage or exudate (purulent cellulitis) 4
• Penetrating trauma or injection drug use 1, 2
• Evidence of MRSA infection elsewhere in the body 1
• Known nasal colonization with MRSA 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy 4

MRSA-Active Antibiotic Options

When MRSA coverage is indicated, choose from these oral options: 4

• Clindamycin 300-450 mg three times daily (covers both streptococci and MRSA as monotherapy) 4, 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin, amoxicillin, or penicillin) for dual streptococcal and MRSA coverage 4, 1
• Doxycycline or minocycline PLUS a beta-lactam 4
• Linezolid 600 mg twice daily (covers both streptococci and MRSA) 4

Important Caveat About TMP-SMX

TMP-SMX alone does NOT adequately cover streptococci, so it must be combined with a beta-lactam for typical cellulitis 4, 1. However, in high MRSA-prevalence areas like Hawaii, TMP-SMX monotherapy showed 91% success rates, significantly better than cephalexin alone (74%) 7.

Penicillin Allergy Alternatives

For patients with penicillin allergy: 1, 2

• Clindamycin is the preferred option, as 99.5% of S. pyogenes strains remain susceptible 1
• Levofloxacin 500 mg daily is an alternative fluoroquinolone option 2
• Avoid fluoroquinolones unless beta-lactams are contraindicated 2

Severe or Complicated Cellulitis Requiring Hospitalization

For hospitalized patients with complicated skin and soft tissue infections, use IV antibiotics with MRSA coverage: 4

• IV vancomycin (most commonly recommended) 4
• Linezolid 600 mg IV/PO twice daily 4, 8
• Daptomycin 4 mg/kg IV once daily 4
• Telavancin 10 mg/kg IV once daily 4
• Clindamycin 600 mg IV/PO three times daily (if local resistance rates <10%) 4
• Treat for 7-14 days based on clinical response 4

Adjunctive Measures

Always implement these supportive measures alongside antibiotics: 1, 2

• Elevate the affected extremity to promote drainage of edema 1, 2
• Treat predisposing conditions such as tinea pedis, toe web abnormalities, venous insufficiency, or trauma 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to hasten resolution 1, 2

Common Pitfalls to Avoid

• Do not routinely prescribe MRSA-active antibiotics for typical non-purulent cellulitis without risk factors 1, 6
• Do not use TMP-SMX as monotherapy for typical cellulitis unless in a high MRSA-prevalence area with purulent features 4, 7
• Do not fail to examine interdigital toe spaces for fissuring or maceration that may harbor pathogens 2
• Do not use rifampin as monotherapy or adjunctive therapy for cellulitis 4
• Do not obtain routine blood cultures or tissue aspirates for typical cellulitis; reserve for patients with malignancy, severe systemic features, or immunocompromise 2