Antibiotic Treatment for Uncomplicated Cellulitis

For uncomplicated cellulitis, a 5-day course of antibiotics active against streptococci is the recommended first-line treatment. 1, 2

First-Line Antibiotic Options

Cephalexin 500 mg orally four times daily for 5 days is recommended as first-line therapy for uncomplicated cellulitis 2, 3
Penicillin or amoxicillin can be used when streptococcal coverage is the primary concern 2, 3
Dicloxacillin is recommended when staphylococcal coverage is needed 2
Clindamycin 300-450 mg orally four times daily for 5 days is recommended for penicillin-allergic patients 2, 3

A 5-day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis if clinical improvement occurs within the first 5 days 1, 4
The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5-7 days 1
Multiple studies support the efficacy of short-course therapy, with similar clinical outcomes between 5-day and 10-day treatment durations 4

Cellulitis is primarily caused by beta-hemolytic streptococci, with Staphylococcus aureus less frequently involved unless associated with penetrating trauma or an underlying abscess 3, 5
MRSA is an unusual cause of typical cellulitis, and standard beta-lactam therapy is successful in 96% of typical cellulitis cases 2

Consider MRSA coverage only in specific situations, such as:
- Cellulitis associated with penetrating trauma 1, 2
- Evidence of MRSA infection elsewhere 2, 3
- Nasal colonization with MRSA 2
- Injection drug use 2, 3
- Systemic inflammatory response syndrome 2
- Purulent drainage 2, 3
- High local prevalence of community-associated MRSA 6
When MRSA coverage is needed, options include:
- Trimethoprim-sulfamethoxazole 2, 6
- Doxycycline 2
- Clindamycin (covers both streptococci and MRSA) 2, 6

Elevate the affected area to promote drainage of edema and inflammatory substances 2, 3
Treat underlying conditions that may predispose to infection, such as tinea pedis, venous eczema/stasis dermatitis, or lymphedema 2, 3

Keep skin well hydrated with emollients 2
Reduce underlying edema through elevation, compression stockings, or diuretic therapy if appropriate 2, 3
For frequent infections despite preventive measures, prophylactic antibiotics may be considered 2, 3

Failure to examine interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens 3
Not elevating the affected area, which delays improvement 3
Inadequate treatment duration when clinical improvement is not evident after 5 days 1, 3
Unnecessary use of broad-spectrum antibiotics for typical uncomplicated cellulitis 2, 5
Failure to distinguish cellulitis from purulent collections, as the latter requires drainage rather than antibiotics alone 2