Summary:

Cellulitis is an infection of the soft tissue deep to the skin that results in erythema, inflammation, tenderness, and pain. It is most commonly caused by Streptococcus pyogenes or staphylococcus aureus. Other etiology bacteria include haemophilus influenza, streptococcus pneumonia, gram negative, and anaerobic species. The treatment is with antibiotics targeted at the suspected etiologic organism. Cephalexin is standard for non-purulent cellulitis, with coverage for methicillin-resistant staphylococcus aureus being necessary in the setting of purulence. Duration and intravenous (IV) versus oral anti- microbial therapy is dependent on the clinical severity

Microbiology

• Beta-hemolytic streptococcus species
• Staphylococcus aureus
  • Most common organism in abscesses with the exception or perioral or perirectal locations
  • Large burden of methicillin-resistance Staphylococcus aureus (MRSA)
• Specific situations
  • Pasteurella multocida in the setting of animal bites
  • Aeromonas hydrophila and Vibro vulnificus in water exposure
  • Clostridium species in gas gangrene

Clinical Presentation

• Presents as a local area of erythema, warmth, tenderness, and pain
• Typically unilateral
• Lower extremities are the most common location
• Skin should be inspected for areas of breakdown, including maceration
  • Other predisposing conditions include lymphedema, venous insufficiency, immunocompromise, tinea infections

Risk Factors & Transmission

• Any skin disruption, such as tinea, ulcers, or wounds
• Prior cellulitis
• Venous insufficiency or impaired lymphatic drainage
• Chronic edema
• Obesity
• Injection drug use

Differential Diagnosis

• Erysipelas | Has sharply demarcated and raised borders
• Necrotizing fasciitis
• Gas gangrene
• Varicella zoster
• Stasis dermatitis
  • Typically both lower legs unlike unilateral presentation in cellulitis
• Septic arthritis or bursitis
  • Consider if located near a relevant structure
• Gout
  • Consider if clearly inflamed joint or a prior history of similar symptoms
• Insect bite
  • Some bites can be associated with large local reactions, e.g., Lyme disease (without typical ‘bullseye’ pattern)
  • Outdoor activity or unusual location for cellulitis may point to Lyme

Diagnosis

• Clinical diagnosis suspected when there is an appropriate history and physical exam
• Identify if any abscess is present either clinically or with ultrasound

Treatment

• Incise and drain any detectible abscess  
• Culture any abscess, although deferral is reasonable in a typical case
  • Skin cultures of non-purulent cellulitis are not recommended
• Mark the leading edge of erythema

Antibiotic choice depends on location of care and suspected etiologic agent (see below)

• Location of care
  • Admission is indicated for systemic signs, intractable pain, suspicion of deep space infection, immunocompromise, or failed outpatient treatment
  • Admission requires intravenous antibiotics and blood cultures are recommended
  • Transition to an appropriate oral agent may occur after clinical improvement
• Etiologic agent
  • Purulent infections must consider agent active against MRSA
  • Perirectal, perioral, or pressure ulcers require MRSA, gram-negative, and anaerobic coverage pending culture results
• See below for antibiotic choices

Duration

• Uncomplicated cellulitis: 5 days of therapy is sufficient if clinical improvement has occurred
• Admitted patients: Up to 14 days may be required depending on clinical course

Antibiotics list

Purulent infection, with or without abscess (MRSA coverage needed)

• Oral agents
  • Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets BID
  • Doxycycline 100 mg BID
  • Clindamycin 300-450 mg QID
• Intravenous agents
  • Vancomycin dosed per hospital protocol
  • Linezolid 600 mg every 12 hours
  • Daptomycin 4 mg/kg every 24 hours

Non-purulent infection (coverage for MRSA considered if risk factors)

• Oral agents
  • Cephalexin 500 mg QID
  • Dicloxacillin 500 mg QID
  • Clindamycin 300-450 mg QID
  • Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets BID
• Intravenous agents
  • Cefazolin 1 g every 8 hours
  • Nafcillin or oxacillin 1 g every 8 hours
  • Clindamycin 600 mg every 8 hours

Learn More – Primary Sources

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Disease Society of America

NICE Guideline: Cellulitis and erysipelas: antimicrobial prescribing (2019)

Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians (2021)

CDC: Cellulitis

Related ObG Topics:

ACP Guidelines: Best Practices for Use of Short-Duration Antibiotics for Common Infections

Herpes Zoster: Clinical Presentation and Treatment

Lyme Disease: Diagnosis and Treatment