Treatment of Cellulitis
For uncomplicated cellulitis, treat with oral antibiotics targeting streptococci (such as cephalexin 500 mg four times daily, penicillin, amoxicillin, dicloxacillin, or clindamycin) for 5 days, extending treatment only if no improvement occurs by day 5. 1
Antibiotic Selection Based on Severity
Mild Nonpurulent Cellulitis
- Use antibiotics active against streptococci as first-line therapy, including penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin 1, 2
- β-hemolytic Streptococcus is the most common causative organism in typical cellulitis cases 3
- Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors 2, 4
Moderate to Severe Nonpurulent Cellulitis
- Expand coverage to include both streptococci and methicillin-susceptible S. aureus (MSSA) 1
- Consider agents like cephalexin or dicloxacillin that cover both organisms 1
When to Add MRSA Coverage
Add MRSA-active antibiotics (trimethoprim-sulfamethoxazole or clindamycin) only in specific high-risk situations: 2
- Cellulitis associated with penetrating trauma 2
- Evidence of MRSA infection elsewhere 2
- History of injection drug use 2, 3
- Purulent drainage present 2
- Systemic inflammatory response syndrome (SIRS) 2
- Athletes, prisoners, military recruits, long-term care facility residents, or prior MRSA exposure 3
Important caveat: A randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin for typical nonpurulent cellulitis provided no additional benefit (85% vs 82% cure rate, p=0.66) 4. However, in MRSA-prevalent areas, antibiotics targeting MRSA showed significantly higher success rates than cephalexin alone (91% vs 74%, p<0.001) 5.
Treatment Duration
- Treat for 5 days if clinical improvement occurs 1, 2
- Extend treatment beyond 5 days only if the infection has not improved within the initial treatment period 1, 2
- This shorter duration is as effective as traditional 10-day courses for uncomplicated cases 2
Treatment Setting Determination
Outpatient Management (Most Cases)
Treat as outpatient if the patient lacks: 1
- Systemic inflammatory response syndrome (SIRS) 1, 2
- Altered mental status 1, 2
- Hemodynamic instability 1, 2
Hospitalization Criteria
Admit patients with any of the following: 1, 2
- Concern for deeper or necrotizing infection 1, 2
- Poor adherence to therapy 1, 2
- Severe immunocompromise 1, 2
- Failing outpatient treatment 1
- Presence of SIRS, altered mental status, or hemodynamic instability 1, 2
Diagnostic Testing
- Do not routinely obtain blood cultures or tissue aspirates for typical cellulitis cases 1, 2
- Obtain blood cultures only for patients with: 1
- Most cellulitis cases (85%) are nonculturable, making routine cultures low-yield 3
Adjunctive Measures
- Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1, 2
- Treat predisposing factors including edema, obesity, eczema, venous insufficiency, and toe web abnormalities 1, 2
- Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to reduce inflammation 2
Prevention of Recurrent Cellulitis
Address Underlying Risk Factors
- Identify and treat predisposing conditions at the initial diagnosis, including tinea pedis, chronic edema, cutaneous lesions, and venous insufficiency 1, 6
Prophylactic Antibiotics
For patients with 3-4 episodes per year despite treatment of predisposing factors, consider prophylaxis with: 1, 2
Common Pitfalls to Avoid
- Don't automatically extend treatment to 10 days if clinical improvement occurs by day 5 2
- Don't add MRSA coverage reflexively for typical nonpurulent cellulitis without specific risk factors 2, 4
- Don't ignore treatment failure with first-line antibiotics—consider resistant organisms, conditions mimicking cellulitis, or underlying complications like immunosuppression 3
- Don't forget to assess for necrotizing soft tissue infections, which require urgent surgical intervention 7