First-Line Treatment for Cellulitis
For typical uncomplicated cellulitis, use beta-lactam monotherapy with oral agents such as cephalexin, penicillin, amoxicillin, dicloxacillin, or clindamycin for 5 days, as MRSA coverage is unnecessary in 96% of cases. 1, 2
Antibiotic Selection
Standard First-Line Agents
- Beta-lactam monotherapy is the standard of care for typical non-purulent cellulitis because streptococci and methicillin-sensitive Staphylococcus aureus are the predominant pathogens 1, 2
- Recommended oral options include:
Why MRSA Coverage Is Usually Unnecessary
- Beta-lactam treatment succeeds in 96% of patients, confirming MRSA is an uncommon cause of typical cellulitis 1, 2
- A prospective study demonstrated that adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases 2
- Combination therapy with SMX-TMP plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without purulent drainage 1, 2
Treatment Duration
- Treat for 5 days if clinical improvement has occurred, extending only if symptoms have not improved 1, 2, 3
- This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases 2
- The American College of Physicians and IDSA both support this shortened duration based on RCT evidence showing equivalent outcomes 1, 2
When to Add MRSA Coverage
Specific Risk Factors Requiring Dual Coverage
Add MRSA coverage only when cellulitis is associated with: 1, 2, 3
- Penetrating trauma, especially from injection drug use
- Purulent drainage present
- Evidence of MRSA infection elsewhere or nasal colonization
- Systemic inflammatory response syndrome (fever, tachycardia, hypotension)
Combination Regimens When MRSA Coverage Needed
- Oral options: SMX-TMP plus a beta-lactam (cephalexin, penicillin, or amoxicillin), OR doxycycline plus a beta-lactam 1, 2
- Clindamycin monotherapy covers both streptococci and MRSA, avoiding the need for true combination therapy 1, 2
- Critical caveat: Doxycycline and SMX-TMP lack reliable activity against beta-hemolytic streptococci and must never be used as monotherapy for typical cellulitis 1, 2
Severe Infections Requiring IV Therapy
- Hospitalize and use IV antibiotics for patients with systemic toxicity (high fever, hypotension, altered mental status), rapid progression, or suspected necrotizing fasciitis 2, 3
- Recommended IV regimens: Vancomycin or linezolid plus piperacillin-tazobactam, a carbapenem, or ceftriaxone and metronidazole 2
- For documented group A streptococcal necrotizing fasciitis, use penicillin plus clindamycin specifically 2
Adjunctive Measures
- Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1, 2, 3
- Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 2, 3
- Treat predisposing conditions such as tinea pedis, venous insufficiency, eczema, and toe web abnormalities to prevent recurrence 1, 2, 3
Diagnostic Approach
- Cellulitis is a clinical diagnosis based on acute onset of erythema, warmth, swelling, and tenderness 4, 5, 6
- Blood cultures, tissue aspirates, or skin biopsies are unnecessary for typical cases 1, 3
- Obtain blood cultures only for patients with malignancy, severe systemic features (high fever, hypotension), or unusual predisposing factors (immersion injury, animal bites, neutropenia, severe immunodeficiency) 1
Common Pitfalls to Avoid
- Don't extend treatment beyond 5 days if clinical improvement has occurred 2, 3
- Don't automatically add MRSA coverage for typical non-purulent cellulitis without specific risk factors 2, 3
- Don't use doxycycline or SMX-TMP as monotherapy for typical cellulitis, as streptococcal coverage will be inadequate 1, 2
- Don't confuse cellulitis with pseudocellulitis (venous stasis dermatitis, contact dermatitis, eczema, lymphedema), which are frequently misdiagnosed as cellulitis 6, 7