Initial Treatment for Knee Cellulitis
For typical knee cellulitis, start with oral antibiotics targeting streptococci—specifically penicillin, amoxicillin, cephalexin, dicloxacillin, or clindamycin—and treat for 5 days if clinical improvement occurs. 1
Antibiotic Selection Algorithm
First-Line Therapy (Typical Cellulitis)
- Target streptococci as the primary pathogen since β-hemolytic Streptococcus causes the majority of identified cellulitis cases 1, 2
- Appropriate oral antibiotics include:
- Penicillin
- Amoxicillin
- Amoxicillin-clavulanate
- Cephalexin
- Dicloxacillin
- Clindamycin 1
- Most patients can receive oral therapy from the start without requiring intravenous antibiotics 1
When to Add MRSA Coverage
MRSA is an unusual cause of typical cellulitis and routine coverage is unnecessary 1. However, consider adding MRSA-active antibiotics if:
- Penetrating trauma present, especially from illicit drug use 1
- Purulent drainage visible 1
- Concurrent MRSA infection elsewhere 1
- High-risk populations: athletes, prisoners, military recruits, long-term care residents, prior MRSA exposure, or intravenous drug users 2
For MRSA coverage when needed:
- Oral options: Trimethoprim-sulfamethoxazole (SMX-TMP), doxycycline, or clindamycin 1
- Intravenous options: Vancomycin, daptomycin, linezolid, or telavancin 1
- If covering both streptococci and MRSA orally, use clindamycin alone OR combine SMX-TMP or doxycycline with a β-lactam (penicillin, cephalexin, or amoxicillin) 1
Critical Evidence on MRSA Treatment
A prospective study demonstrated that β-lactams (cefazolin or oxacillin) succeeded in 96% of cellulitis cases, confirming MRSA is uncommon in typical cellulitis 1. Additionally, a double-blind trial showed SMX-TMP plus cephalexin was no more effective than cephalexin alone in pure cellulitis without abscess or purulent drainage 1.
Treatment Duration
- 5 days of antibiotics is as effective as 10 days if clinical improvement occurs by day 5 1
- Extend treatment duration if infection has not improved at 5 days 1, 3
- A retrospective study of hospitalized cellulitis showed average treatment duration of 2 weeks, though this may represent more severe cases 1
Adjunctive Measures
Elevation
- Elevate the affected knee to promote gravity drainage of edema and inflammatory substances, which hastens improvement 1, 3
Anti-inflammatory Therapy
- Systemic corticosteroids (prednisone 40 mg daily for 7 days) can be considered in non-diabetic adults, though this is a weak recommendation 1, 3
- A pilot study showed adding ibuprofen 400 mg every 6 hours for 5 days significantly shortened time to inflammation regression and complete resolution 4
Address Predisposing Factors
- Treat tinea pedis or other toe web abnormalities aggressively 1, 3
- Manage venous insufficiency with compression and elevation 3
- Apply daily emollients to prevent skin dryness and cracking 3
Common Pitfalls to Avoid
Unnecessary MRSA Coverage
In the absence of abscess, ulcer, or purulent drainage, β-lactam monotherapy is recommended 1. Avoid unnecessarily broad antibiotics when typical cellulitis features are present without MRSA risk factors 3.
Inadequate Treatment Duration
While 5 days is sufficient for improved cases, failing to extend therapy when infection persists leads to treatment failure 1, 3.
Ignoring Worsening After Treatment Initiation
Some patients experience worsening cutaneous inflammation and systemic features after starting antibiotics due to sudden pathogen destruction releasing inflammatory enzymes—this does not necessarily indicate treatment failure 1.
Not Obtaining Cultures When Indicated
Blood cultures are unnecessary for typical cellulitis but should be obtained if the patient has malignancy, severe systemic features (high fever, hypotension), neutropenia, severe immunodeficiency, or unusual exposures like immersion injury or animal bites 1.
When to Consider Hospitalization
Hospitalize if: