Antibiotic Treatment for Cellulitis
For typical non-purulent cellulitis, start with a 5-day course of an oral antibiotic active against streptococci: cephalexin, amoxicillin, dicloxacillin, or penicillin are first-line choices. 1
Treatment Algorithm Based on Clinical Presentation
Mild, Non-Purulent Cellulitis (Most Common)
- Begin with streptococcal-targeted therapy using cephalexin, amoxicillin, dicloxacillin, or penicillin for 5 days 1
- Beta-hemolytic streptococci are the primary pathogens in typical cellulitis, with S. aureus less frequently involved unless there is penetrating trauma or an underlying abscess 1
- Extend treatment beyond 5 days only if no clinical improvement is evident 1
- For penicillin-allergic patients, use clindamycin or erythromycin 1, 2
When to Add MRSA Coverage
Add MRSA-active antibiotics only when specific risk factors are present, not routinely 1:
- Penetrating trauma
- Evidence of MRSA infection elsewhere or nasal colonization
- Injection drug use
- Purulent drainage
- Systemic inflammatory response syndrome (SIRS)
- Athletes, prisoners, military recruits, long-term care residents, or men who have sex with men 3
For MRSA coverage, choose one of these regimens 1:
- Clindamycin alone (covers both streptococci and MRSA)
- TMP-SMX plus a beta-lactam (such as amoxicillin or cephalexin)
- A tetracycline plus a beta-lactam
Severe Cellulitis Requiring Hospitalization
- Use IV vancomycin for empiric MRSA coverage pending culture data 1
- Alternative IV options include linezolid, daptomycin, or telavancin 1
- For severely compromised patients, use vancomycin plus piperacillin-tazobactam or a carbapenem 1
- Treatment duration is 7-14 days, individualized based on clinical response 1
Evidence Supporting Short-Course Therapy
- Multiple studies demonstrate that 5-6 days of appropriate antibiotics achieve similar clinical outcomes to longer courses 1
- The American College of Physicians and NICE guidelines both support 5-7 day treatment durations 1
- In a Hawaii study with 62% MRSA prevalence, TMP-SMX achieved 91% success versus 74% for cephalexin, demonstrating the importance of local resistance patterns 4
Critical Pitfalls to Avoid
- Do not routinely cover MRSA in typical cellulitis—this is the most common error, leading to unnecessary broad-spectrum antibiotic use 1, 3
- Always examine interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens and serve as entry points 1
- Elevate the affected extremity—failure to do so delays clinical improvement 1
- Do not obtain cultures routinely in typical cases; reserve blood cultures for patients with malignancy, severe systemic features, or unusual predisposing factors 1
Adjunctive Measures
- Elevate the affected area to promote drainage of edema 1, 5
- Treat predisposing conditions including tinea pedis, toe web abnormalities, edema, and venous insufficiency 1
- Consider prednisone 40 mg daily for 7 days in non-diabetic adults to hasten resolution 1, 5