Cellulitis Treatment
First-Line Antibiotic Therapy
For uncomplicated cellulitis, treat with oral antibiotics active against streptococci—specifically 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
Key Antibiotic Selection Principles:
Target streptococci as the primary pathogen in typical non-purulent cellulitis, as β-hemolytic Streptococcus is the most common causative organism 1, 3, 4
MRSA coverage is NOT routinely needed for uncomplicated cellulitis and should be reserved for specific high-risk scenarios 1, 4
Oral therapy is as effective as IV therapy for uncomplicated cases—macrolides/streptogramins have demonstrated superiority over IV penicillin in comparative trials 5
Duration of Treatment
5 days of antibiotics is as effective as 10 days if clinical improvement has occurred by day 5 1, 6, 2
Extend treatment beyond 5 days only if infection has not improved within this initial period 1, 2
This shorter duration reduces unnecessary antibiotic exposure without compromising outcomes 1
When to Add MRSA Coverage
Consider adding MRSA-targeted therapy ONLY in these specific situations: 1, 2
- Cellulitis associated with penetrating trauma 1, 2
- Purulent drainage present 1, 2
- Concurrent evidence of MRSA infection elsewhere in the body 1, 2
- History of injection drug use 2
- High-risk populations: athletes, prisoners, military recruits, long-term care residents, men who have sex with men 3
MRSA coverage options include: 2
- Clindamycin alone
- Combination of trimethoprim-sulfamethoxazole (SMX-TMP) or doxycycline with a β-lactam
Moderate Infections with Systemic Signs
For patients with systemic signs of infection (fever, tachycardia, hypotension), provide coverage for both streptococci AND methicillin-susceptible S. aureus (MSSA) with agents such as cefazolin or nafcillin 1, 6
Essential Adjunctive Measures
Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances—particularly important in older adults with venous insufficiency 1, 6, 2
Identify and treat predisposing conditions including tinea pedis, toe web abnormalities, venous eczema, trauma, obesity, and lymphedema 1, 6, 2, 7
Systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients to reduce inflammation and hasten resolution 1, 6, 2
Hospitalization Criteria
Admit patients with any of the following: 1, 6, 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, treat as outpatient 1
Prevention of Recurrent Cellulitis
Address underlying predisposing factors such as edema, venous insufficiency, tinea pedis, and toe web abnormalities at the time of initial diagnosis 1, 2, 7
For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics such as oral penicillin, erythromycin, or intramuscular benzathine penicillin 1, 6, 2
Blood Cultures
Obtain blood cultures only in patients with: 1
- Malignancy
- Severe systemic features
- Unusual predisposing factors
Blood cultures are not routinely indicated for uncomplicated cellulitis 1
Critical Pitfalls to Avoid
Don't automatically extend treatment to 10 days if clinical improvement has occurred by day 5—this is unnecessary antibiotic exposure 2
Don't add MRSA coverage for typical non-purulent cellulitis without specific risk factors—MRSA is an unusual cause of typical cellulitis 1, 2, 4
Don't forget to examine interdigital toe spaces in lower-extremity cellulitis, as treating fissuring or maceration reduces recurrence 2
Don't overlook elevation of the affected area, especially in patients with venous insufficiency or lymphedema 2
Consider pseudocellulitis mimickers such as venous stasis dermatitis, contact dermatitis, eczema, and lymphedema if patients fail to respond to appropriate first-line antibiotics 3, 4