What is the recommended treatment for cellulitis?

Treatment of Cellulitis

For uncomplicated cellulitis, start with oral antibiotics targeting streptococci (penicillin, amoxicillin, cephalexin, or clindamycin) for 5 days if clinical improvement occurs by day 5. 1, 2

First-Line Antibiotic Selection

Streptococcal coverage is the cornerstone of treatment since β-hemolytic Streptococcus causes the majority of identifiable cellulitis cases. 3

Standard Regimens (No MRSA Risk Factors):

• Cephalexin 500 mg orally four times daily for 5 days 1
• Penicillin or amoxicillin if streptococcal infection is strongly suspected 2
• Dicloxacillin or amoxicillin-clavulanate for broader coverage including methicillin-sensitive S. aureus 1, 2
• Clindamycin 300-450 mg orally four times daily for penicillin-allergic patients or after recent beta-lactam therapy to avoid resistance 1, 2

When to Add MRSA Coverage:

Add MRSA-active antibiotics when specific risk factors are present: 1, 2

• Penetrating trauma (especially injection drug use)
• Purulent drainage present
• Evidence of MRSA infection elsewhere or nasal colonization
• Systemic inflammatory response syndrome (SIRS)
• Lack of response to beta-lactam antibiotics after 24-48 hours
• High-risk populations: athletes, children in daycare, men who have sex with men, prisoners, military recruits, long-term care residents 3

For MRSA coverage, use combination therapy:

• Outpatient: Trimethoprim-sulfamethoxazole, doxycycline, or clindamycin PLUS a beta-lactam for streptococcal coverage 1, 2
• Inpatient: Vancomycin, linezolid, daptomycin, or telavancin 2, 4

Duration of Treatment

A 5-day course is as effective as 10 days if clinical improvement has occurred by day 5. 1, 2 This represents strong evidence from the American College of Physicians and Infectious Diseases Society of America. 1

• Extend treatment beyond 5 days only if the infection has not improved 1
• Expect clinical improvement within 24-48 hours of starting appropriate antibiotics 1

Essential Adjunctive Measures

Elevation of the affected area is crucial and often neglected - it promotes gravity drainage of edema and inflammatory substances. 1, 2

Additional supportive care:

• Treat predisposing conditions: tinea pedis, venous eczema, trauma, or other skin conditions 1, 2
• Examine interdigital toe spaces in lower extremity cellulitis to identify and treat fissuring, scaling, or maceration that harbors pathogens 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to hasten resolution 1, 2

Hospitalization Criteria

Admit patients with: 1

• SIRS, altered mental status, or hemodynamic instability
• Concern for deeper or necrotizing infection
• Severe immunocompromise
• Poor adherence to outpatient therapy
• Failure of outpatient treatment

Common Pitfalls to Avoid

Do not routinely order blood cultures or skin biopsies for typical cellulitis cases. 2 Reserve blood cultures for patients with malignancy, severe systemic features, unusual predisposing factors, or immunocompromise. 1

Expect initial worsening after starting antibiotics - cutaneous inflammation may temporarily worsen due to sudden pathogen destruction releasing inflammatory enzymes. 2 This does not indicate treatment failure.

MRSA is an unusual cause of typical cellulitis - avoid empiric MRSA coverage unless specific risk factors are present, as unnecessary broad-spectrum antibiotics drive resistance. 2, 3

Prevention of Recurrent Cellulitis

Each cellulitis episode causes lymphatic damage that increases recurrence risk. 1

Preventive measures:

• Treat interdigital maceration and keep skin well-hydrated with emollients 1, 2
• Reduce underlying edema through elevation, compression stockings, or diuretics if appropriate 1, 2
• For frequent recurrences despite preventive measures, consider prophylactic antibiotics: monthly intramuscular benzathine penicillin or oral erythromycin 250 mg or penicillin V 1 g twice daily 1, 2

Oral vs. Intravenous Therapy

Oral antibiotics are sufficient for most uncomplicated cellulitis cases. 2 In fact, oral macrolides have demonstrated superior effectiveness compared to intravenous penicillin in clinical trials. 5 The majority (89.7%) of patients in pivotal trials received IV medication exclusively, but this does not indicate superiority over oral therapy for appropriate candidates. 4