What is the first-line treatment for cellulitis (cellulitis diagnosis)?

First-Line Treatment for Cellulitis

For typical uncomplicated cellulitis, initiate treatment with an oral antibiotic active against streptococci—specifically penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin—for 5 days, extending only if clinical improvement is not evident. 1

Pathogen-Directed Approach

The treatment strategy hinges on understanding the causative organisms:

• Beta-hemolytic streptococci are the primary pathogens in typical cellulitis, with Staphylococcus aureus less frequently involved unless there is penetrating trauma or an underlying abscess 1, 2
• In non-purulent cellulitis, the clinical isolation rate of a pathogen is less than 20%, leaving the diagnosis unconfirmed in 80% of cases 3
• The majority of non-purulent, uncomplicated cellulitis cases are caused by β-hemolytic streptococci or methicillin-sensitive S. aureus 4

Treatment Algorithm by Clinical Presentation

Mild, Uncomplicated Cellulitis (Outpatient)

First-line options targeting streptococci:

• Penicillin, amoxicillin, dicloxacillin, or cephalexin for 5 days 1
• A penicillinase-resistant semisynthetic penicillin or first-generation cephalosporin should be selected 3
• For penicillin-allergic patients: clindamycin or erythromycin 3, 1
• Levofloxacin is a viable alternative for patients with penicillin allergy, though fluoroquinolones should be reserved for patients with allergies to beta-lactams 1

When to Add MRSA Coverage

Do NOT routinely cover MRSA in typical non-purulent cellulitis 4. However, add MRSA coverage for specific high-risk scenarios:

• Penetrating trauma 1
• Evidence of MRSA elsewhere or nasal colonization 1
• Injection drug use 1, 2
• Purulent drainage 1
• Systemic inflammatory response syndrome (SIRS) 1
• High-risk populations: athletes, children in daycare, men who have sex with men, prisoners, military recruits, long-term care facility residents, prior MRSA exposure 2

If MRSA coverage is needed:

• Clindamycin alone, OR 1
• TMP-SMX or a tetracycline in combination with a beta-lactam (such as amoxicillin) 1

Moderate to Severe Cellulitis (May Require Hospitalization)

• Systemic antibiotics with coverage for streptococci and consideration of adding coverage against methicillin-susceptible S. aureus 1
• For severe cellulitis requiring hospitalization: vancomycin or another antimicrobial effective against both MRSA and streptococci 1
• For severely compromised patients: vancomycin plus either piperacillin-tazobactam or imipenem/meropenem 1
• Treatment duration for severe cellulitis is 7-14 days, individualized based on clinical response 1

Treatment Duration

• 5 days is the recommended duration for uncomplicated cellulitis, with extension only if no improvement is seen 1
• The American College of Physicians recommends a 5- to 6-day course of antibiotics active against streptococci for nonpurulent cellulitis 1
• The National Institute for Health and Care Excellence guideline recommends 5 to 7 days 1
• For complicated skin and skin structure infections, the protocol-defined duration ranged from 7 to 28 days in controlled trials 5

Diagnostic Considerations

• Cellulitis is a clinical diagnosis based on acute onset of redness, warmth, swelling, tenderness, and pain 4
• Cultures are NOT routinely recommended for typical cases, as aspiration of skin is not helpful in 75-80% of cases and blood cultures are rarely positive (<5% of cases) 3, 1
• Obtain blood cultures only in patients with: malignancy, severe systemic features, or unusual predisposing factors 1

Adjunctive Measures Critical for Success

• Elevate the affected area to promote gravity drainage of edema and inflammatory substances 1
• Examine and treat interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens—this is a commonly missed step 1
• Treat predisposing conditions such as edema, tinea pedis, obesity, venous insufficiency, or other toe web abnormalities 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adult patients to hasten resolution 1

Prevention of Recurrence

• Identify and treat predisposing conditions at the time of initial diagnosis 1, 6
• For patients with 3-4 episodes per year despite addressing predisposing factors: consider prophylactic antibiotics such as oral penicillin or erythromycin twice daily for 4-52 weeks 1

Critical Pitfalls to Avoid

• Failure to examine interdigital toe spaces for fissuring, scaling, or maceration 1
• Not elevating the affected area, which delays improvement 1
• Inadequate treatment duration when clinical improvement is not evident after 5 days—extend therapy rather than switching antibiotics prematurely 1
• Overuse of MRSA coverage in typical non-purulent cellulitis without risk factors 4
• Failure to consider cellulitis mimickers such as venous stasis dermatitis, contact dermatitis, eczema, lymphedema, or erythema migrans when patients fail to respond to appropriate first-line antibiotics 2, 4