What is the recommended treatment for cellulitis?

Cellulitis Treatment

For uncomplicated cellulitis, treat with oral antibiotics active against streptococci (penicillin, amoxicillin, cephalexin 500mg four times daily, dicloxacillin, or clindamycin) for 5 days, extending only if no clinical improvement occurs by day 5. 1

First-Line Antibiotic Selection

The Infectious Diseases Society of America establishes that streptococcal coverage is the cornerstone of cellulitis treatment, as β-hemolytic Streptococcus causes the majority of identifiable cases. 1, 2

Recommended first-line agents include: 1, 3

• Penicillin
• Amoxicillin
• Amoxicillin-clavulanate
• Dicloxacillin
• Cephalexin (500 mg four times daily)
• Clindamycin

For moderate infections with systemic signs (fever, tachycardia, elevated white count), broaden coverage to include both streptococci and methicillin-susceptible S. aureus (MSSA) with agents like cefazolin or nafcillin. 1

Treatment Duration

A 5-day course is as effective as 10 days if clinical improvement has occurred by day 5. 1, 3 This is a critical point that prevents unnecessary antibiotic exposure. Extend treatment only if the infection has not improved within the initial 5-day period. 3

MRSA Coverage: When to Add It

MRSA is an unusual cause of typical non-purulent cellulitis and routine coverage is unnecessary. 1, 4 However, add MRSA coverage specifically in these situations: 1, 3

• Penetrating trauma
• Purulent drainage present
• Concurrent MRSA infection elsewhere
• History of injection drug use
• Athletes, prisoners, military recruits, long-term care residents, or prior MRSA exposure 2

MRSA coverage options include: 3

• Clindamycin alone, OR
• Combination of trimethoprim-sulfamethoxazole (SMX-TMP) or doxycycline with a β-lactam

Essential Adjunctive Measures

Elevation of the affected extremity is critical to promote gravity drainage of edema and inflammatory substances, particularly in older adults with venous insufficiency. 1, 3

Identify and treat predisposing conditions: 1, 3

• Tinea pedis and toe web abnormalities (examine interdigital spaces in all lower-extremity cellulitis)
• Venous insufficiency and lymphedema
• Trauma or skin breakdown
• Eczema or venous stasis dermatitis

Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adult patients to reduce inflammation and hasten resolution. 1, 3 This is supported by evidence showing faster resolution with anti-inflammatory therapy. 5

Hospitalization Criteria

Admit patients with any of the following: 1, 3

• Systemic inflammatory response syndrome (SIRS)
• Altered mental status
• Hemodynamic instability
• Concern for deeper or necrotizing infection
• Severe immunocompromise
• Failure of outpatient treatment
• Poor adherence anticipated

Otherwise, outpatient oral therapy is appropriate for uncomplicated cases. 1

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors, initiate prophylactic antibiotics (oral penicillin, erythromycin, or intramuscular benzathine penicillin). 1, 3

Address underlying conditions aggressively: treat tinea pedis, manage venous insufficiency and lymphedema, and maintain skin integrity. 3, 6

Critical Pitfalls to Avoid

• Don't extend treatment beyond 5 days if clinical improvement has occurred - this leads to unnecessary antibiotic exposure. 3
• Don't automatically add MRSA coverage for typical non-purulent cellulitis without specific risk factors. 3, 4
• Don't forget to examine interdigital toe spaces in lower-extremity cellulitis, as treating fissuring or maceration reduces recurrence. 3
• Don't overlook elevation of the affected area, especially in patients with venous insufficiency or lymphedema. 3

When to Obtain Blood Cultures

Blood cultures should be obtained only in patients with malignancy, severe systemic features, or unusual predisposing factors, as they are low-yield in typical cellulitis. 1

Failure to Improve

If the patient fails to improve with appropriate first-line antibiotics, consider resistant organisms, conditions that mimic cellulitis (venous stasis dermatitis, contact dermatitis, eczema, lymphedema), or underlying complicating conditions such as immunosuppression, chronic liver disease, or chronic kidney disease. 2, 4