Cellulitis Treatment
First-Line Antibiotic Therapy
For uncomplicated cellulitis, treat with oral antibiotics active against streptococci—such as penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin (500 mg four times daily), or clindamycin—for 5 days, extending only if clinical improvement has not occurred. 1, 2
Antibiotic Selection Algorithm
Uncomplicated cellulitis (no systemic signs): Use streptococcal-targeted therapy only 1, 3
Moderate infections with systemic signs: Add coverage for both streptococci and MSSA 1
- Consider cefazolin or nafcillin for inpatient therapy 5
Treatment Duration
- 5 days of antibiotics is as effective as 10 days if clinical improvement occurs by day 5 1, 2
- Extend treatment only if infection has not improved within the initial 5-day period 2
- This shorter duration reduces unnecessary antibiotic exposure without compromising outcomes 1
MRSA Coverage: When to Add It
MRSA is an unusual cause of typical non-purulent cellulitis and does not require routine coverage. 1, 3
Specific Indications for MRSA Coverage
Add MRSA-targeted therapy only when these risk factors are present: 1, 2
- Penetrating trauma
- Purulent drainage
- Concurrent evidence of MRSA infection elsewhere
- History of injection drug use
- Athletes, prisoners, military recruits, or long-term care facility residents 4
MRSA Treatment Options
- Clindamycin alone 2
- Combination of trimethoprim-sulfamethoxazole (SMX-TMP) or doxycycline with a β-lactam 2
Adjunctive Measures
Elevation of the affected extremity is essential to promote gravity drainage of edema and inflammatory substances. 1, 2
Additional Supportive Care
- Treat predisposing conditions: tinea pedis, venous eczema, trauma, toe web abnormalities 1, 2
- Systemic corticosteroids: Consider prednisone 40 mg daily for 7 days in non-diabetic adults to reduce inflammation and hasten resolution 1, 2, 6
- One small study showed that adding NSAIDs (ibuprofen 400 mg every 6 hours for 5 days) significantly shortened time to resolution 6
Hospitalization Criteria
Admit patients with any of the following: 1, 2
- Systemic inflammatory response syndrome (SIRS)
- Altered mental status
- Hemodynamic instability
- Concern for deeper or necrotizing infection
- Severe immunocompromise
- Poor adherence to outpatient therapy
- Failure of outpatient treatment
Otherwise, manage as outpatient with oral antibiotics. 1
Prevention of Recurrent Cellulitis
Address Underlying Risk Factors
- Identify and treat: edema, obesity, eczema, venous insufficiency, lymphedema, toe web abnormalities 1, 2
- Examine interdigital toe spaces in lower-extremity cellulitis—treating fissuring or maceration reduces recurrence 2, 7
Prophylactic Antibiotics
For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics: 1
Diagnostic Considerations
- Cellulitis is a clinical diagnosis based on acute onset of erythema, warmth, swelling, tenderness, and pain 4, 3
- Blood cultures should be obtained only in patients with malignancy, severe systemic features, or unusual predisposing factors 1
- Microbiological diagnosis is often unobtainable—only 15% of cases yield positive cultures 4
Common Pitfalls to Avoid
- Don't extend treatment beyond 5 days if clinical improvement has occurred 2
- Don't automatically add MRSA coverage for typical non-purulent cellulitis without specific risk factors 2, 3
- Don't overlook cellulitis mimickers: venous stasis dermatitis, contact dermatitis, eczema, lymphedema, and erythema migrans can appear similar 3
- Don't forget to examine toe web spaces in lower-extremity cellulitis 2
- Don't neglect elevation of the affected area, especially in older adults with venous insufficiency 2
Failure to Improve
If the patient fails to respond to appropriate first-line antibiotics, consider: 4
- Resistant organisms (including MRSA)
- Secondary conditions mimicking cellulitis
- Underlying complicating conditions: immunosuppression, chronic liver disease, chronic kidney disease