What is the treatment for cellulitis?

Treatment of Cellulitis

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage is NOT routinely necessary. 1

Recommended Oral Agents

• Cephalexin 500 mg orally every 6 hours (four times daily) for 5 days is the preferred first-line agent for typical nonpurulent cellulitis 1, 2
• Dicloxacillin 250-500 mg every 6 hours provides excellent streptococcal and MSSA coverage 1, 3
• Amoxicillin, amoxicillin-clavulanate, or penicillin are equally appropriate alternatives 1
• Clindamycin 300-450 mg orally every 6 hours covers both streptococci and MRSA if local resistance is <10% 1

Recommended IV Agents for Hospitalized Patients

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for hospitalized patients requiring parenteral therapy 1
• Nafcillin 2 g IV every 6 hours or oxacillin 2 g IV every 6 hours are alternatives 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 4

• Five-day courses are as effective as 10-day courses for uncomplicated cellulitis based on high-quality randomized controlled trial evidence 1, 4
• Clinical resolution at 14 days with no relapse by 28 days occurred in 98% of patients receiving 5 days versus 98% receiving 10 days 4
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1

Common pitfall: Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 1

When to Add MRSA Coverage

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

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, hypotension, or altered mental status 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA Coverage Options

When MRSA coverage is indicated:

• Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA (use only if local resistance <10%) 1
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin, amoxicillin, or penicillin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1

Critical caveat: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1

Severe Cellulitis Requiring Hospitalization

Indications for Hospitalization

Admit patients with any of the following: 1

• SIRS criteria (fever, tachycardia, hypotension, altered mental status) 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1
• Failure of outpatient treatment after 24-48 hours 1

IV Antibiotic Regimens for Severe Infections

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: 1

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

Treatment duration for severe cellulitis is 7-10 days, not the standard 5 days, with reassessment at 5 days. 1

Transition to Oral Therapy

• Patients can transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 1
• Oral options include cephalexin, dicloxacillin, or clindamycin 1

Essential Adjunctive Measures

Elevation of the affected extremity is critical and often neglected—it hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1

• Elevate the limb above heart level for at least 30 minutes three times daily 1
• Examine interdigital toe spaces carefully for tinea pedis, fissuring, scaling, or maceration 1
• Treat predisposing conditions including venous insufficiency, lymphedema, eczema, chronic edema, and obesity 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Critical caveat: Avoid systemic corticosteroids in diabetic patients despite potential benefit in non-diabetics 1

Special Populations

Diabetic Foot Cellulitis

Diabetic patients with foot cellulitis require broader coverage and longer duration: 1

• Mild infections: dicloxacillin, clindamycin, cephalexin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, or levofloxacin 1
• Moderate infections: amoxicillin-clavulanate, levofloxacin, ceftriaxone, ampicillin-sulbactam, or ertapenem 1
• Severe infections: piperacillin-tazobactam, imipenem-cilastatin, or vancomycin plus ceftazidime with or without metronidazole 1
• Median treatment duration extends beyond the standard 5-day course 1

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours is the optimal choice for patients allergic to both penicillins and cephalosporins 1
• Provides single-agent coverage for both streptococci and MRSA without requiring combination therapy 1
• Use only if local MRSA clindamycin resistance rates are <10% 1

Pediatric Cellulitis

• Cephalexin 25 mg/kg/day in four divided doses for typical nonpurulent cellulitis 1
• For hospitalized children: vancomycin 15 mg/kg IV every 6 hours as first-line therapy 1
• Alternative: clindamycin 10-13 mg/kg/dose IV every 6-8 hours if stable, no bacteremia, and local resistance <10% 1
• Never use doxycycline in children under 8 years of age due to tooth discoloration and bone growth effects 1

Prevention of Recurrent Cellulitis

Annual recurrence rates are 8-20% in patients with previous leg cellulitis. 1

• Treat tinea pedis and interdigital toe web abnormalities 1
• Manage venous insufficiency with compression stockings once acute infection resolves 1
• Reduce lymphedema 1
• Keep skin well hydrated with emollients 1

For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics: 1

• Oral penicillin V 250 mg twice daily for 4-52 weeks 1
• Oral erythromycin 250 mg twice daily 1
• Intramuscular benzathine penicillin every 2-4 weeks 1

Monitoring and Treatment Failure

• Reassess within 24-48 hours for outpatients to ensure clinical improvement 1
• If no improvement with appropriate first-line antibiotics, consider resistant organisms (especially MRSA), cellulitis mimickers (DVT, necrotizing fasciitis), or underlying complications 1, 5
• Blood cultures are positive in only 5% of cases and are unnecessary for typical cellulitis 1
• Obtain blood cultures only in patients with severe systemic features, malignancy, neutropenia, or unusual predisposing factors 1

Warning signs requiring immediate surgical consultation: 1

• Severe pain out of proportion to examination findings 1
• Skin anesthesia 1
• Rapid progression or "wooden-hard" subcutaneous tissues 1
• Gas in tissue or bullous changes 1
• Systemic toxicity with hypotension or altered mental status 1