What is the recommended treatment for cellulitis?

Cellulitis Treatment

First-Line Antibiotic Therapy

For uncomplicated cellulitis, treat with a 5-day course of oral antibiotics targeting streptococci, such as penicillin, amoxicillin, cephalexin (500 mg four times daily), dicloxacillin, or clindamycin, extending treatment only if clinical improvement has not occurred by day 5. 1, 2

The Infectious Diseases Society of America and American College of Physicians emphasize that typical cellulitis is predominantly caused by β-hemolytic streptococci and methicillin-sensitive S. aureus (MSSA), not MRSA. 1, 3, 4 This is critical because many clinicians over-treat with MRSA coverage unnecessarily.

Antibiotic Selection Algorithm:

Uncomplicated cases (no systemic signs):

• Penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, cephalexin, or clindamycin 1, 2
• These agents provide adequate streptococcal coverage for the majority of cases 1

Moderate infections with systemic signs (fever, tachycardia):

• Consider dual coverage for both streptococci and MSSA 1
• Options include cefazolin or nafcillin for inpatient therapy 5

Duration of Treatment

A 5-day antibiotic course is as effective as 10 days if clinical improvement occurs by day 5. 1, 2 This shorter duration reduces antibiotic exposure, costs, and resistance development while maintaining equivalent efficacy. 1

• Extend treatment beyond 5 days only if infection has not improved 1, 2
• Do not automatically prescribe 10-14 day courses as was traditional practice 2

MRSA Coverage: When to Add It

MRSA coverage is NOT routinely needed for typical non-purulent cellulitis. 1, 4 Despite rising community-acquired MRSA rates, it remains an unusual cause of classic cellulitis. 1

Add MRSA coverage ONLY when these specific risk factors are present:

• Penetrating trauma 1, 2
• Purulent drainage 1, 2
• Concurrent MRSA infection elsewhere 1, 2
• History of injection drug use 2
• Athletes, prisoners, military recruits, long-term care residents, or prior MRSA exposure 3

MRSA coverage options:

• Clindamycin alone 2
• Trimethoprim-sulfamethoxazole (SMX-TMP) or doxycycline combined with a β-lactam 2

Essential Adjunctive Measures

Elevation of the affected extremity is critical to promote gravity drainage of edema and inflammatory substances. 1, 2 This is particularly important in older adults with venous insufficiency. 2

Identify and treat predisposing conditions:

• Tinea pedis and toe web abnormalities (examine interdigital spaces) 1, 2
• Venous insufficiency and lymphedema 1, 2
• Trauma, eczema, or venous stasis dermatitis 1, 6

Systemic corticosteroids may be considered:

• Prednisone 40 mg daily for 7 days in non-diabetic adults 2
• Can reduce inflammation and hasten resolution 1, 2
• Some evidence suggests anti-inflammatory therapy shortens time to complete resolution 7

Hospitalization Criteria

Admit patients with any of the following:

• Systemic inflammatory response syndrome (SIRS) 1, 2
• Altered mental status 1, 2
• Hemodynamic instability 1, 2
• Concern for deeper or necrotizing infection 1, 2
• Severe immunocompromise 1
• Failure of outpatient treatment 1, 2
• Poor adherence to therapy 1, 2

Otherwise, treat as outpatient. 1

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics:

• Oral penicillin 1, 2
• Erythromycin 5, 2
• Intramuscular benzathine penicillin 5, 2

Address underlying conditions aggressively:

• Treat tinea pedis and toe web maceration 1, 2
• Manage edema, obesity, venous insufficiency 1, 2
• Control eczema and chronic skin conditions 1

Common Pitfalls to Avoid

Don't automatically prescribe 10-day courses when 5 days with clinical improvement is sufficient. 2

Don't add MRSA coverage reflexively for typical non-purulent cellulitis without specific risk factors. 1, 2, 4

Don't forget to examine toe web spaces in lower extremity cellulitis, as treating fissuring reduces recurrence. 2

Don't overlook elevation of the affected area, especially in patients with venous disease. 2

Don't obtain blood cultures routinely unless the patient has malignancy, severe systemic features, or unusual predisposing factors. 1

When to Reassess

If no improvement occurs within 48-72 hours on appropriate antibiotics, consider:

• Resistant organisms (though still uncommon) 3
• Pseudocellulitis mimickers (venous stasis dermatitis, contact dermatitis, eczema, lymphedema) 4
• Underlying complicating conditions (immunosuppression, chronic liver disease, chronic kidney disease) 3
• Deeper infection requiring imaging 6