Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. The borders are not clearly delineated. The lower extremities are the most frequent site of infection, but cellulitis can occur anywhere on the body. Diagnosis is usually clinical, and management involves oral and/or parenteral antibiotics. Coverage for MRSA may be added, depending on the presence of risk factors.

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Cellulitis is inflammation of the skin and subcutaneous tissues. It is often due to infection.

Epidemiology and etiology

  • Incidence: 200 cases per 100,000 patient-years
  • More common in middle-aged and older populations
  • Lower extremities: most common site
  • Most common agents: 
    • Staphylococcus aureus:
      • MSSA
      • MRSA
    • Group A Streptococcus (Streptococcus pyogenes)
  • Less common agents: 
    • Pasteurella multocida (from animal bites)
    • Aeromonas hydrophila and Vibrio vulnificus (after water exposure)
    • Clostridium species (myonecrosis)
    • Pseudomonas aeruginosa (in immunocompromised patients)
    • Erysipelothrix rhusiopathiae (occupational exposure in butchers, slaughterhouse workers, farmers, veterinarians)

Risk factors

  • Breach of the skin barrier (wounds, ulcers, insect/animal bites)
  • Skin inflammation (psoriasis, eczema)
  • Injuries contaminated with dirt or seawater
  • Preexisting infection (tinea, varicella)
  • Previous history of cellulitis
  • Crush injuries
  • Second- and third-degree burns
  • Frostbite
  • Lymphedema or any obstruction of lymphatic drainage
  • Immunodeficiency
  • Diabetes mellitus
  • Obesity
  • Venous insufficiency

Pathophysiology and Clinical Presentation


  • Bacteria enter disrupted skin barrier:
    • Through minor cuts or injuries
    • May be secondary to a distant site or systemic infection
    • In some cases, portal of entry is not evident.
  • Invasion of dermis and subcutaneous tissue triggers cytokine release, recruiting neutrophils and other inflammatory cells to the site.
  • Intrinsic bacterial factors allow the pathogen to evade initial host defenses, leading to erythema, pain, and local swelling of the skin (edema).
  • In immunocompromised patients, infection is limited eventually to the area of invasion.
  • If the pathogen overcomes the immune defenses, further spread (deeper and/or contiguous infection and bacteremia in immunodeficiency) occurs.
  • Reduced control of infection occurs in:
    • Decreased tissue vascularity and oxygenation
    • Increased peripheral fluid stasis
    • Poor ability to combat infections (e.g., diabetes)

Clinical findings

  • Prodromal systemic symptoms:
    • May have signs of toxicity (fever > 100.5℉ (38℃), chills, and tachycardia)
    • Muscle and joint pain
    • Headache
  • Local features:
    • Indurated lesions or edematous area with erythema and poorly defined borders
    • Spreading redness or lesions
    • Pain and tenderness in the affected area
    • Tight, glossy, swollen skin or dimpling (noted in edema surrounding hair follicles)
    • May present with purulent exudate (usually associated with S. aureus)
    • An abscess may also be found (collection of pus within the dermis or subcutaneous layer).
  • Associated signs and symptoms:
    • Regional lymph node swelling and tenderness (lymphadenitis)
    • Severe infections:
      • Can present with general malaise, fatigue, dizziness, confusion, muscle and joint pain, and diaphoresis
      • Can have blistering lesions or bullae formation


  • Diagnosis of cellulitis is clinical:
    • Edema
    • Erythema
    • Warmth
    • Tenderness
    • Associated lymphadenopathy
  • Symptoms, risk factors, and progression of the skin lesion aid in ruling out differential diagnoses.
  • Laboratory tests are nonspecific:
    • Leukocytosis (common in all infections)
    • ↑ Inflammatory markers:
      • Erythrocyte sedimentation rate (ESR)
      • CRP levels
  • Microbiologic studies: 
    • Wound culture: used to identify pathogens and guide antibiotic therapy
    • Blood culture: obtained in cases suggestive of bacteremia and/or in severely immunodeficient patients
  • Imaging:
    • Ultrasonography (US) is used to rule out abscess.
    • Complicated skin and soft tissue infections need to be further evaluated.
      • Orbital and sinus CT to determine extent of orbital cellulitis and presence of an abscess
      • MRI and/or bone scintigraphy may be performed in cases of severe joint pain to confirm/rule out septic arthritis or osteomyelitis.

Management and Complications

Treatment approach

  • Supportive care:
    • Symptomatic treatment for fever, local pain, and aches
    • Adequate hydration and elevation of the affected lower limb
  • Empiric therapy covers group A Streptococcus and MSSA.
  • Determination of risk factors and need for parenteral therapy:
    • MRSA risk factors:
      • Recent hospitalization or surgery (≤ 2 months ago)
      • Hemodialysis
      • Residence in a long-term care facility
      • HIV infection
      • Prior episode of MRSA
      • Recent antibiotic use without MRSA coverage
      • Indwelling medical device
    • Need for parenteral therapy:
      • Inability to tolerate oral intake
      • Systemic signs of toxicity
      • Rapid progression of erythema
      • Cellulitis over a medical device (vascular graft or prosthetic joint)
      • Failure to respond to prior oral antibiotics

Treatment regimen

  • No MRSA risk factors:
    • Oral therapy (mild infection):
      • Dicloxacillin
      • Amoxicillin
      • Cephalexin
      • Clindamycin
    • Parenteral therapy:
      • Cefazolin
      • Nafcillin
      • Oxacillin
      • Clindamycin
  • With MRSA risk factors:
    • Oral therapy:
      • Trimethoprim–sulfamethoxazole
      • Amoxicillin plus doxycycline
      • Amoxicillin plus minocycline
      • Clindamycin
    • Parenteral therapy:
      • Vancomycin
      • Daptomycin
  • Other considerations:
    • Bite wounds: add anaerobic coverage
    • Hospitalization:
      • Usually required for facial lesions because of high risk of spread of infection to the CNS (meningitis, encephalitis)
      • For those with concomitant conditions such as hepatic, renal, or cardiac failure
    • Severe progressive infections: might require surgical debridement of necrotic tissue or abscesses
Left lower leg and knee cellulitis

Cellulitis in the left lower leg and knee:
Left: Local swelling with salmon-pink skin discoloration and local warmth is evident.
Right: leg after 6 weeks of antibiotic therapy

Image: “Helicobacter cinaedi bacteremia with cellulitis in a living-donor kidney transplant recipient identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a case report” by BMC Research Notes. License: CC BY 4.0


  • Abscess: 
    • Collection of pus in the dermis or subcutaneous tissue
    • Presents as a tender, fluctuant, erythematous swelling or discrete nodule
    • Treatment: incision and drainage of drainable abscess detected on exam or US
  • Necrotizing fasciitis:
    • Deep infection associated with rapid destruction and necrosis of the fascia and subcutaneous tissues
    • Life-threatening
  • Septic arthritis:
    • Infection in a joint, frequently secondary to bacteria
    • Develops from hematogenous seeding but can also arise from extension of infection from the skin/soft tissue
  • Osteomyelitis
    • Infection of the bone
    • Poorly healing skin and soft tissue infections are at risk.
  • Sepsis:
    • Potentially life-threatening organ dysfunction caused by a dysregulated host response to infection
    • Presentation can include fever, tachycardia, tachypnea, hypotension, and/or altered mentation.
    • Immunocompromised patients with skin infections are at risk for this condition.

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Differential Diagnosis

  • Erysipelas: an acute superficial infection of the upper dermis and lymphatics, usually caused by group A beta-hemolytic Streptococcus: This condition presents as a sharply demarcated, raised skin lesion, with erythema, edema, and warmth.
  • Necrotizing fasciitis: a rapidly progressive infection resulting in extensive necrosis of subcutaneous tissue, fascia, and muscle: Necrotizing fasciitis is most commonly caused by group A Streptococcus but often involves other types of bacteria in a mixed infection. The condition presents with necrosis, crepitus, bullae, and purple skin discoloration.
  • Dermatitis: general term for edematous skin rash caused by an allergic reaction, irritant, or infection
  • Folliculitis: a localized inflammation of the hair follicle or sebaceous glands that is primarily caused by S. aureus: Presentation includes erythema, papules, pustules, and tenderness of the affected area.
  • Impetigo: a highly contagious skin infection of the upper epidermis: Impetigo commonly affects children < 5 years of age and is caused by S. aureus or group A Streptococcus. Patients present with an erythematous area covered in small vesicles, pustules, and/or honey-colored crusts.
  • Staphylococcal scalded skin syndrome: a toxin-mediated blistering skin disorder caused by S. aureus. Presentation includes diffuse cutaneous erythema, tenderness, bullae formation, and superficial desquamation (sloughing off of the superficial layer of skin, leaving a red “scalded” appearance). The mucous membranes are spared.


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  2. Kalyanakrishnan R, Salinas R, Higuita N (2015). Skin and soft tissue infections. Am Fam Physician. 92(6),474–483.
  3. Klotz C, et al. (2019). Adherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcome. Eur J Clin Microbiol Infect Dis. 38(4),703–709.
  4. Spelman D, Baddour LM (2020). Cellulitis and skin abscess in adults: Treatment. UpToDate. Retrieved January 30, 2021, from https://www.uptodate.com/contents/cellulitis-and-skin-abscess-in-adults-treatment
  5. Spelman D, Baddour LM (2020). Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis. UpToDate. Retrieved January 30, 2021, from https://www.uptodate.com/contents/cellulitis-and-skin-abscess-epidemiology-microbiology-clinical-manifestations-and-diagnosis
  6. Stevens DL, et al. (2014). Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 59(2),e10–52.

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