What is cellulitis and what are the risks and treatment options?

Cellulitis: Definition, Risks, and Treatment

What is Cellulitis?

Cellulitis is an acute bacterial infection of the deep dermis and subcutaneous tissue that presents with rapidly spreading erythema, warmth, swelling, and tenderness, most commonly affecting the lower extremities. 1 The skin surface may exhibit a characteristic "peau d'orange" (orange peel) appearance due to superficial edema surrounding hair follicles. 1 Vesicles, bullae, and cutaneous hemorrhage (petechiae or ecchymoses) may develop in more severe cases. 1

Key Distinguishing Features

• Cellulitis is NOT appropriate terminology for infections with pus collections (abscesses, furuncles, septic bursitis) - these require drainage as primary treatment, not antibiotics alone. 1
• The infection involves deeper layers than erysipelas, which is limited to the upper dermis and superficial lymphatics. 1
• Systemic manifestations include fever, tachycardia, confusion, hypotension, and leukocytosis, which may appear hours before visible skin changes. 1

Causative Organisms

Most cellulitis cases are caused by β-hemolytic streptococci (especially Group A Streptococcus) and methicillin-sensitive Staphylococcus aureus (MSSA). 1 Blood cultures are positive in only 5% of cases, and needle aspiration yields organisms in 5-40% of cases. 1 The majority of cellulitis cases are non-culturable, making the causative bacteria unknown in approximately 85% of cases. 2

Pathogen Sources

• Streptococci frequently originate from macerated or fissured interdigital toe spaces (tinea pedis), emphasizing the critical importance of examining and treating toe web abnormalities. 1
• The anal canal or vagina may serve as reservoirs, particularly for Group B streptococci in patients with previous gynecologic cancer treated with surgery and radiation. 1
• S. aureus more commonly causes cellulitis associated with penetrating trauma, including injection drug use sites. 1

Risk Factors and Predisposing Conditions

Major Risk Factors

• Disruption of lymphatic drainage from surgical procedures including saphenous venectomy, axillary node dissection for breast cancer, and gynecologic malignancy operations with lymph node dissection (especially when followed by radiation therapy). 1
• Chronic conditions: venous insufficiency, lymphedema, obesity, eczema, diabetes mellitus. 1
• Skin barrier disruption: tinea pedis, toe web abnormalities, chronic wounds, acute trauma. 1
• Immunosuppression: severe cell-mediated immunodeficiency, neutropenia, chronic liver disease, chronic kidney disease. 1, 2

Special Circumstances Requiring Broader Coverage

• Penetrating trauma (especially illicit drug injection sites). 1
• Animal bites: Pasteurella species (especially P. multocida) or Capnocytophaga canimorsus from cat/dog bites. 1
• Water exposure: Aeromonas hydrophila (fresh water), Vibrio species including V. vulnificus (saltwater in warm climates). 1

Diagnostic Approach

When to Obtain Cultures

Cultures of blood, tissue aspirates, or skin biopsies are unnecessary for typical cellulitis cases. 1 However, obtain blood cultures and consider skin biopsy or aspirate cultures for patients with:

• Malignancy. 1
• Severe systemic features (high fever, hypotension). 1
• Unusual predisposing factors (immersion injury, animal bites, neutropenia, severe immunodeficiency). 1

Common Diagnostic Pitfalls

Many conditions mimic cellulitis, including venous stasis dermatitis, contact dermatitis, deep vein thrombosis, panniculitis, eczema, lymphedema, and erythema migrans. 3, 4 Misdiagnosis leads to unnecessary hospital admissions and antibiotic overuse, as most alternative diagnoses are non-infectious. 5

Treatment Algorithm

Outpatient Oral Therapy (Mild Cases)

For typical uncomplicated cellulitis without systemic inflammatory response syndrome (SIRS), altered mental status, or hemodynamic instability, start oral antibiotics targeting streptococci. 1

First-line oral options:

• Penicillin, amoxicillin, or amoxicillin-clavulanate. 1
• Dicloxacillin or cephalexin. 1
• Clindamycin (if penicillin allergy). 1

Treatment duration: 5 days is as effective as 10 days if clinical improvement occurs by day 5. 1 Extend therapy if infection has not improved. 1

Inpatient Parenteral Therapy (Severe Cases)

Hospitalize patients with SIRS, altered mental status, hemodynamic instability, concern for deeper/necrotizing infection, poor adherence, severe immunosuppression, or failed outpatient treatment. 1

Parenteral options:

• Nafcillin (penicillinase-resistant penicillin) or cefazolin (first-generation cephalosporin). 1
• For life-threatening penicillin allergies: clindamycin or vancomycin. 1

MRSA Coverage - When to Add It

MRSA is an unusual cause of typical cellulitis and routine coverage is NOT recommended. 1 A prospective study showed 96% success with β-lactams (cefazolin/oxacillin) alone, confirming MRSA cellulitis is uncommon. 1

Add MRSA coverage ONLY for cellulitis associated with:

• Penetrating trauma, especially illicit drug injection. 1
• Purulent drainage. 1
• Evidence of MRSA infection elsewhere or nasal colonization. 1
• SIRS (severe nonpurulent cellulitis). 1
• High-risk populations: athletes, children in daycare, men who have sex with men, prisoners, military recruits, long-term care residents, prior MRSA exposure. 2

MRSA-active options:

• Intravenous: vancomycin, daptomycin, linezolid, or telavancin. 1
• Oral: doxycycline, clindamycin, or trimethoprim-sulfamethoxazole. 1

Severe/Complicated Infections

For severely compromised patients or suspected necrotizing infection, use broad-spectrum coverage: vancomycin PLUS piperacillin-tazobactam or a carbapenem (imipenem/meropenem). 1 Obtain prompt surgical consultation for aggressive infections with systemic toxicity or suspicion of necrotizing fasciitis. 1

Adjunctive Measures

Essential Management Steps

• Elevate the affected area. 1
• Carefully examine interdigital toe spaces and treat fissuring, scaling, or maceration to eradicate pathogen colonization and reduce recurrence. 1
• Treat predisposing conditions: edema, obesity, eczema, venous insufficiency, toe web abnormalities. 1

Corticosteroid Consideration

Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in nondiabetic adult patients with cellulitis. 1 One randomized, double-blind, placebo-controlled trial showed that an 8-day tapering course starting with 30 mg prednisolone attenuated inflammatory worsening after antibiotic initiation and hastened resolution. 1

Common Pitfall

Cutaneous inflammation sometimes worsens after initiating antibiotic therapy due to sudden pathogen destruction releasing potent inflammatory enzymes - this does not indicate treatment failure. 1

Prevention of Recurrent Cellulitis

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

• Oral penicillin or erythromycin twice daily for 4-52 weeks. 1
• Intramuscular benzathine penicillin every 2-4 weeks. 1
• Continue prophylaxis as long as predisposing factors persist. 1

Address underlying conditions during both acute episodes and as routine care to minimize recurrence risk. 1