Skin and soft tissue infections

Skin and soft tissue infections (SSTIs) are a group of heterogeneous conditions affecting the epidermis, dermis, subcutaneous tissue, or superficial fascia. Uncomplicated infections are most commonly caused by gram-positive pathogens (Streptococcus, Staphylococcus) that infiltrate the skin after minor injuries (e.g., scratches, insect bites). Complicated infections have a higher tendency to be polymicrobial. SSTIs primarily manifest with painful, warm, erythematous skin lesions and may also lead to purulent fluid collections and/or necrosis of the affected tissue. Systemic symptoms like fever are usually a sign of more severe infections. Risk factors for developing SSTIs (or more severe forms of SSTIs) include diabetes mellitus, immunodeficiency, and chronic edema. Diagnosis is mostly clinical but some patients may require imaging or laboratory studies. Purulent infections, such as abscesses, are primarily treated with incision and drainage while nonpurulent infections (e.g., erysipelas, cellulitis) require antibiotic therapy. Necrotizing soft tissue infections (NSTIs) have a high mortality rate; they are a surgical emergency and require immediate wound debridement.

Tissue involvement of SSTI (from superficial to deep): impetigo (superficial epidermis), erysipelas (superficial dermis and lymphatic vessels), cellulitis (deep dermis and subcutaneous tissue), necrotizing fasciitis (subcutaneous tissue including superficial and deep fascia)

Cardinal signs of inflammation

• Rubor = redness
• Calor = heat
• Tumor = swelling/edema
• Dolor = pain
• Functio laesa = loss of function

Risk factors for skin and soft tissue infections ^[1]

• Local factors
  • Chronic lymphedema
  • Local skin defects (e.g., tinea pedis)
  • Circulatory disorders: arteriovenous insufficiency, chronic edema, stasis
  • Peripheral neuropathy, paresis
• Systemic factors
  • Diabetes mellitus
  • Immunodeficiency (e.g., HIV infection, asplenia, chemotherapy)
  • Chronic kidney disease (leading to, e.g., chronic edema, dialysis)
  • Obesity, poor nutritional status
  • Drug or alcohol use disorder
  • Older and younger age
• Increased exposure to pathogens
  • Nosocomial pathogens (e.g., prolonged hospitalization, surgery)
  • Water exposure (e.g., sea water, hot tubs)
  • IV drug use, long-term intravascular devices ^[2]
  • Trauma (e.g., open wounds, exposed fractures)

Complications

• Local spread of infection
• Systemic involvement with fever and possible sepsis (see “Sepsis” for details on the management of severe infections)
• Spread of infection to distant sites (see “Staphylococcal infections”)

Management

Definitions ^[3][4]

• Erysipelas: superficial skin infection involving the upper dermis
• Cellulitis: local infection of the deep dermis and subcutaneous tissue

Clinical features ^[3][4]

• Local signs: erythema, edema, warmth, tenderness
  • Specific to erysipelas: raised, sharply demarcated lesion
  • Specific to cellulitis: poorly defined lesion with induration
• Cutaneous lymphatic edema (historically referred to as “peau d'orange”)
• Common locations: lower limbs, face
• Possible additional features
  • Lymphangitis: red streaks radiating from the skin lesion and following the direction of the lymphatic vessels
  • Lymphadenitis: swollen, tender, regional lymph nodes
  • Bullae
  • Purulent exudate
• Systemic symptoms (in moderate/severe infections): fever, chills, confusion, nausea, headache, muscle and joint pain

Bilateral cellulitis is exceedingly rare. Patients presenting with bilateral leg erythema should also be evaluated for alternative diagnoses, including stasis dermatitis and lymphedema. ^[5]

Pathophysiology ^[3][4]

• Entry is commonly via a minor skin injury ; erysipelas can consequently spread via superficial lymphatic vessels.
• May also be secondary to a systemic infection

In both erysipelas and cellulitis, the most common point of entry for the pathogen is a small skin lesion (e.g., interdigital tinea pedis).

Etiology ^[3][4]

• Beta-hemolytic streptococci: mostly group A Streptococcus (S. pyogenes)
• Less common pathogens for cellulitis
  • S. aureus
  • Pasteurella multocida (gram-negative, encapsulated coccobacillus): secondary to dog and cat bites

GAS is the most common cause of nonpurulent skin and soft tissue infections (i.e., erysipelas, cellulitis).

Diagnostics ^[3][6]

Diagnosis is usually clinical. In patients with systemic symptoms, laboratory studies, cultures, and imaging may be indicated to assess severity and tailor treatment.

• Laboratory studies
  • CBC: possible leukocytosis
  • BMP: signs of underlying conditions that are risk factors for infections (e.g., diabetes mellitus, chronic kidney disease)
  • Inflammatory markers; (e.g., CRP, procalcitonin): may be elevated
• Imaging
  • Soft tissue ultrasound
    • Indication: consider if there is suspicion for skin abscess and/or foreign body (see “Purulent SSTI” section)
    • Findings: hypoechoic strands (signs of edema) between subcutaneous fat tissue ^[7]
  • CT/MRI with or without IV contrast: consider if there is concern for complications (e.g., pyomyositis, osteomyelitis) ^[6]
• Microbiology: Gram stain and cultures are not routinely recommended. ^[3]
  • Consider skin biopsy, aspirate, and/or blood cultures in patients with the following: ^[3]
    • Malignancy or patients receiving chemotherapy
    • Neutropenia
    • Severe immunodeficiency
    • Immersion injuries
    • Animal bites

Treatment of nonpurulent SSTIs ^[1][3][8]

General principles

• Empiric antibiotic therapy active against streptococci and S. aureus is the mainstay of treatment for nonpurulent SSTIs.
• Treatment should also include the control of any predisposing factors (e.g., edema, fungal infections).
• The majority of patients with cellulitis or erysipelas are clinically stable and can be managed as outpatients.
• Patients with systemic symptoms often require hospitalization and parenteral antibiotic therapy.
• See “Sepsis” for further details on the management of severe infections.

Antibiotic therapy

• Systemic antibiotic therapy is usually required.
• Empiric regimens should usually cover Streptococcus spp. and S. aureus (see “Antibiotic therapy for skin and soft tissue infections” for detailed recommendations).
• Consider inpatient management with parenteral antibiotics for patients with any of the following:
  • Systemic symptoms
  • Suspicion for deeper infection
  • Immunocompromise
  • Failure of outpatient treatment. ^[3]
• Consider coverage for MRSA in the following cases:
  • Penetrating trauma
  • Evidence of MRSA infection or colonization elsewhere
  • Injection drug use
  • Purulent drainage
  • SIRS

Antibiotics should be targeted against gram-positive pathogens and provide broad-spectrum coverage in severe cases. ^[4]

Supportive care

• Elevation of the affected limbs
• Rest and acute pain management as needed

Acute management checklist for nonpurulent SSTI

• Stabilize the patient as needed.
• Consider indications for laboratory studies and imaging.
• Start empiric antibiotic therapy according to recommendations for severity and risk factors (see “Empiric antibiotic therapy for skin and soft tissue infections”).
• Provide supportive care (limb elevation, pain management).
• Identify and treat the underlying cause, if present (e.g., tinea pedis, poorly controlled diabetes).
• Consider indications for admission/inpatient management.

Subtypes and variants

Perianal streptococcal dermatitis

• Definition: : an infection of the perianal skin with group A Streptococcus characterized by pain, pruritus, and rash
• Epidemiology: most common in children between 6 months and 10 years of age
• Etiology: group A Streptococcus infection
• Clinical features
  • Signs of systemic infection are rare
  • Pruritus, rectal pain, blood-streaked stools
  • Sharply demarcated, erythematous perianal rash with pseudoexudate, crusting, and/or superficial anal fissures/cracks
• Diagnosis: clinical
• Differential diagnosis
  • Candida diaper dermatitis
  • Irritant contact diaper dermatitis
• Treatment: penicillin; in pediatric patients: amoxicillin (oral emulsion is tolerated better)

Other

• Orbital cellulitis; periorbital (preseptal) cellulitis
• Ludwig angina

Complications ^[3][4]

• Recurrent infections
• Abscess
• Infection of deeper tissues: cellulitis, necrotizing fasciitis, osteomyelitis
• Thrombophlebitis, lymphedema
• Systemic complications (e.g., sepsis, endocarditis, streptococcal toxic shock syndrome, poststreptococcal glomerulonephritis, acute rheumatic fever)
• In orbital cellulitis: blindness, cavernous sinus thrombosis, intracranial abscess

Folliculitis, furuncles, and carbuncles ^[3]

• Definitions
  • Folliculitis: localized inflammation of the hair follicle (or sebaceous glands) that is limited to the epidermis
  • Hot tub folliculitis: pseudomonal folliculitis that appears 8–48 hours after exposure to contaminated water; usually a self-limiting condition that does not require antibiotic treatment
  • Furuncle: deep folliculitis beyond the dermis with abscess formation in the subcutaneous tissue
  • Carbuncle: confluent folliculitis that forms an inflammatory mass; abscess and skin necrosis may be present
• Clinical features
  • Tender papules and/or pustules, often pruritic
  • Located at the site of hair follicles
  • Possible pus drainage from follicular orifices
  • Potentially multiple lesions
  • Variable locations (e.g., carbuncles most often develop on the back of the neck)
• Differential diagnoses
  • Ecthyma
  • Acne vulgaris
  • Eosinophilic folliculitis

Facial furuncles can result in severe complications (e.g., periorbital cellulitis, cavernous sinus thrombosis).

Skin abscess ^[3][4]

• Definition: an accumulation of white-yellow pus that contains proteins, leukocytes (especially neutrophils), bacteria, and cellular debris and is located in the dermis and subcutaneous tissue
• Clinical features
  • Cardinal signs of inflammation
  • Painful, tender, and fluctuant red nodules
  • Pain is usually relieved after rupture or drainage.
  • May be surrounded by erythema and induration.
• Differential diagnosis: inflamed epidermoid cyst, carbuncle
• Subtypes and variants
  • Recurrent skin abscess: a new abscess at the site of a previous infection
  • Complex skin abscess: a skin abscess that requires specialized treatment because of its location (e.g., perianal, perirectal), the pathogens involved (e.g., polymicrobial, resistant pathogens), or patient characteristics (e.g., immunodeficiency) ^[4]
  • Scrotal abscess: a subcutaneous collection of pus in the scrotal region, usually a result of inflamed hair follicles
    • Differential diagnoses: neoplasia of the testis, infected hydrocele, genital warts
    • May progress to fournier gangrene.

In both scrotal abscess and epididymitis, the classic signs of inflammation are prominent and help to confirm the diagnosis.

Etiology ^[3]

• S. aureus: most common pathogen for any form of purulent SSTI; MRSA is frequently identified. ^[9][10]
• Streptococcus spp. ^[11]
• P. aeruginosa (e.g., hot tub folliculitis)
• Polymicrobial (e.g., anaerobes or gram-negative bacteria, especially in complex abscesses)
• Noninfectious causes (e.g., ingrown hairs, friction, trauma, or occlusion)
• Fungi (rare): Candida albicans or Malassezia (particularly M. furfur)

Diagnostics ^[1][3]

Diagnosis is usually clinical. In patients with systemic symptoms, laboratory studies, cultures, and imaging may be indicated to assess severity and tailor treatment.

• Laboratory studies
  • CBC: possible leukocytosis
  • BMP: signs of underlying conditions that are risk factors for infections (e.g., diabetes mellitus, chronic kidney disease)
  • Inflammatory markers; (e.g., CRP, procalcitonin) may be elevated
• Imaging ^[6]
  • Soft tissue ultrasound
    • Indications include:
      • Systemic signs of infection (i.e., moderate or severe disease)
      • Confirmation of diagnosis prior to incision and drainage of an abscess
      • Assessment of size, extent, and depth of the abscess ^[12][13]
      • Suspected foreign object at the site of infection (e.g., needle tip, splinter)
      • Suspected complex skin abscess
    • Possible findings ^[7]
      • Skin abscess: hypoechoic, heterogeneous fluid collection with posterior enhancement
      • Surrounding edema (especially in accompanying cellulitis)
  • CT/MRI with or without IV contrast: usually only necessary for complex skin abscesses (e.g., perianal abscess) and the evaluation of complications (e.g., osteomyelitis)
• Microbiology
  • Gram stain and cultures are not routinely recommended, even if CA-MRSA is suspected. ^[1][3][9]
  • Indications for abscess and blood cultures include:
    • Systemic symptoms, severe infections (see “Severity of SSTI”)
    • Immunocompromised patients
    • Recurrent skin abscess
    • Carbuncles
• Additional evaluation: Consider additional evaluation for underlying conditions in patients with recurrent abscess and/or complex skin abscess.
  • Colonization with resistant pathogens (e.g., MRSA)
  • Local causes (e.g., foreign body, pilonidal cyst, hidradenitis suppurativa)
  • Systemic predisposing conditions (e.g., neutrophil disorders)

Treatment of purulent SSTIs

General principles

• Incision and drainage are the mainstay of treatment for purulent SSTIs and are usually sufficient for mild infections.
• Patients with systemic signs of infections require empiric antibiotic therapy.
• Outpatient management is appropriate for clinically stable patients.
• Consider inpatient management for patients with systemic symptoms.
• See “Sepsis” for more details on the management of severe infections.

Interventional therapy ^[3][4]

• Incision and drainage (I&D)
  • Bedside procedure
  • Indications: small skin abscesses carbuncles, large furuncles , inflamed epidermoid cysts
  • See “Abscess incision and drainage” for detailed procedural guidance.
• Surgical drainage
  • Usually performed in the OR
  • Indications can include:
    • Recurrent skin abscesses
    • Multiple abscesses (may be associated with fistulas)
    • Size > 5 cm
    • High-risk anatomical location
    • Suspected mycotic or mycobacterial abscess
    • Comorbidities that increase the risk of complications (e.g., coagulopathy)

Antibiotic therapy ^[3][4]

• Topical antibiotics: Consider in MRSA folliculitis (e.g., mupirocin ). ^[1]
• Systemic antibiotic therapy for purulent SSTIs: Usually not indicated after successful drainage in otherwise healthy individuals. ^{[3][4][14][15]}
  • Indications: moderate/severe infections, recurrent or complex abscesses, according to risk factors and comorbidities (e.g., diabetes mellitus)
  • Regimens often include coverage for MRSA (see “Antibiotic therapy for skin and soft tissue infections” for detailed recommendations).

Mild purulent skin infections usually do not require systemic antibiotic treatment following drainage.

Supportive measures

• Warm compresses (in folliculitis, furuncles, and carbuncles)
• Rest and acute pain management as needed
• Keep the affected area clean and dry. ^[7]
• Consider MRSA decolonization for recurrent abscesses. ^[16]

Acute management checklist for moderate and severe purulent infections

• Stabilize the patient as needed.
• Complete labs and imaging (e.g., soft tissue ultrasound or CT) based on initial results, extension, and location.
• Consider surgery consult if concern for large abscess or severe infection.
• Incision and drainage if indicated; Consider sending fluid samples for Gram stains and cultures.
• Start empiric antibiotic therapy according to recommendations for severity and risk factors (see “Empiric antibiotic therapy for skin and soft tissue infections”).
• Provide symptomatic treatment (e.g., pain management, warm compresses).
• Consider indications for admission/inpatient management.

Definitions ^[3][4]

• Necrotizing soft tissue infection (NSTI): an aggressive, life-threatening infection involving necrosis of the tissue. Superficial and/or deep tissue may be affected (i.e., necrotizing cellulitis, necrotizing fasciitis, necrotizing myositis).
• Necrotizing fasciitis (most common NSTI): a rapidly progressive infection resulting in extensive necrosis of superficial and deep fascia and overlying subcutaneous fat that can develop into a life-threatening condition within hours
• Fournier gangrene: Necrotizing fasciitis of the external genitalia that can spread rapidly to the anterior abdominal wall and gluteal muscles.
• Clostridial myonecrosis: a rapidly spreading necrotizing infection caused by Clostridium perfringens or Clostridium septicum (see “Gas gangrene” for details)

Etiology ^[3][4]

• Aerobic and anaerobic, gram-positive and gram-negative bacteria are frequently isolated.
• Both monomicrobial and polymicrobial causes are common. ; ^[4][17]
  • Polymicrobial: wide variety; of aerobic and anaerobic pathogens, often of intra-abdominal or genitourinary origin (E. coli, Bacteroides spp.)
  • Monomicrobial: commonly group A Streptococcus (S. pyogenes), Peptostreptococcus spp., S. aureus
• Fournier gangrene: usually mixed infection with facultative pathogens (E. coli, Klebsiella, Enterococcus) and anaerobic bacteria

The only way to definitively establish the causative pathogen is by obtaining a deep tissue culture (i.e., during surgical exploration). Clinical features alone are not reliable enough to distinguish between pathogens.

Clinical features ^[3][4]

• Systemic symptoms: fever, chills, altered mental status
• Cutaneous findings
  • Diffuse erythema (often manifests initially as suspected cellulitis that is not responding to initial antibiotic therapy)
  • Extreme tenderness and pain out of proportion to the area of erythema
  • Significant induration of the subcutaneous tissue
  • Crepitus: due to the production of methane and CO₂ by bacteria
  • Purple skin discoloration; (skin necrosis, ecchymosis)
  • Bullae
  • Loss of sensation in the affected area (paresthesias)

Necrotizing fasciitis first spreads along the fascia before spreading to the superficial cutaneous tissue. Local findings may, therefore, be unremarkable, with patients experiencing a disproportionate level of pain.

Red flags that suggest necrotizing deep tissue infection include the presence of crepitus, bullous lesions, skin necrosis, pain out of proportion to examination, and signs of systemic toxicity (especially altered mental status).

Diagnostics ^[3]

A definitive diagnosis is usually made during the visualization of the tissue during surgery.

Do not delay surgical consultation and definitive surgical intervention for imaging and laboratory studies.

• Laboratory studies
  • CBC: leukocytosis
  • BMP: possibly hyperglycemia; renal function may be compromised
  • Inflammatory markers (CRP, ESR; , procalcitonin): elevated
  • CK: elevated
  • Assess organ failure and severity.
• Microbiology
  • Blood cultures (2 sets)
  • Gram stain and cultures from deep tissue ^[3]
• Imaging: not routinely indicated and should not delay treatment ^[4][6]
  • CT/MRI with/without IV contrast ; ^[4]
    • Gas in soft tissue
    • Fascial thickening and edema
    • Lack of contrast enhancement (confirms necrosis)
    • Fluid collections on deep fascial planes
    • Intermuscular septal edema
  • X-ray ^[4]
    • May detect gas in soft tissue
    • The absence of gas does not rule out NSTI.
  • Ultrasound: can identify fluid accumulation and diffuse thickening of the deep tissue ^[4]

Superficial wound cultures may not accurately represent the pathogens found in deep tissue and should not be used to guide management.

Management ^[3][4]

• Admit all patients with suspected or confirmed NSTI to hospital for treatment.
• If clinical features suggest NSTI, start immediate surgical and medical treatment.
  • Surgical exploration with debridement (confirms the diagnosis and the mainstay of treatment)
  • Broad-spectrum antibiotic therapy
• Consult ICU for admission and aggressive supportive care for sepsis, if present. ^[3][4]
  • Provide immediate hemodynamic support: e.g., fluid resuscitation, vasopressors
  • Begin sepsis management.
  • Consider respiratory support as needed, e.g., oxygen therapy, mechanical ventilation.
  • Consider adjuvant therapy on an individual basis (e.g., hyperbaric oxygen, negative pressure wound therapy, intravenous immunoglobulin therapy).

Necrotizing soft tissue infections are a surgical emergency. Expedite and prioritize surgical exploration for diagnostic confirmation and debridement as much as possible!

Surgical exploration and debridement

• Procedure ^[4]
  • Extensive exploration with surgical debridement (removal of necrotic tissue)
  • Obtain deep tissue samples for Gram stain, cultures, and histopathology.
  • Tissue with uncertain perfusion may be left for reassessment on a second intervention.
  • Reexploration every 12–36 hours until there is no evidence of necrotic tissue
• Supportive findings
  • Fascia appears swollen
  • Dull gray fascia; areas of necrosis may be visible
  • Possible brown exudate (no pus)
  • Easy dissection of tissue planes with a blunt instrument or gloved finger

Antibiotic therapy ^[3][4]

• Start systemic, broad-spectrum antibiotic therapy immediately after blood cultures have been obtained.
• See “Antibiotic therapy for skin and soft tissue infections” for detailed recommendations.
  • Consider polymicrobial infections (provide coverage against aerobes, anaerobes, MRSA).
  • If there is evidence of toxic shock syndrome, include antitoxin active antibiotics (e.g., clindamycin, linezolid). ^[4]

Acute management checklist for necrotizing SSTI

• Stabilize the patient as needed (see “Sepsis” for more details on the management of severe infections).
• Consider the need for laboratory and imaging studies.
• Consult surgery, infectious diseases, and intensive care teams immediately.
• Urgent surgical exploration and debridement
• Send deep tissue samples for Gram stain and cultures.
• Aggressive and early empiric antibiotic therapy (see “Empiric antibiotic therapy for skin and soft tissue infections”)
• Admit to intensive care unit.
• Reexploration every 12–36 hours

Complications

• Severe necrosis requiring amputation of the affected limb
• Sepsis
• Disseminated intravascular coagulation
• Organ dysfunction (e.g., acute kidney injury)
• Death: high mortality rate; even with adequate treatment (> 30%) ^[17]

Differential diagnoses

• Gas gangrene: caused by C. perfringens
• Severe SSTI without necrosis

Severity of SSTI ^[3]

Necrotizing infections are always considered severe!

Empiric antibiotic therapy ^[3]

• Choice of empiric antibiotic therapy should include the following factors:
  • Severity (see “SSTI severity grading”)
  • Presence of purulence
  • Local resistance patterns
  • Risk for complications
  • Risk factors for skin and soft tissue infections
• Variants that may require a more specialized treatment include:
  • Bite wounds
  • Recurrent or complex skin abscesses
  • Orbital and periorbital cellulitis
  • Device-associated infections (e.g., dialysis catheters, prosthetic joints)
  • Patients at risk for endocarditis (e.g., patients with a prosthetic heart valve)

Ecthyma gangrenosum

• Definition: an ulcerative lesion extending into the dermis that develops in the setting of bacteremia
• Pathogen: Pseudomonas aeruginosa (not pathognomonic but is the most common causative organism)
• Pathophysiology:
  • Classically develops in patients with P. aeruginosa bacteremia who are immunocompromised
  • Bacteria invade vasculature, causing septic vasculitis and cutaneous necrosis
  • Virulence factors destroy tissue:
    • Exotoxin A: inhibits elongation factor 2, impairing protein synthesis
    • Elastase: degrades elastin in blood vessel walls
    • Phospholipase C: breaks down cell membranes
    • Pyocyanin: produces damaging reactive oxygen species
• Clinical features
  • Rapid progression (within 12–18 hours) of painless red macules → induration, development of pustules, vesicles, and/or bullae → crusted ulcers
  • Can involve skin or mucous membranes; anogenital and axillary areas most commonly involved
  • Can be solitary or multiple
  • Patients typically also systemically ill (e.g., septic shock)
• Diagnosis: primarily a clinical diagnosis
• Treatment: see treatment of skin and soft tissue infections

Erysipeloid

• Definition: cellulitis caused by Erysipelothrix rhusiopathiae
• Pathogen: Erysipelothrix rhusiopathiae, a gram-positive, capsulated bacilli that is found in a variety of animals including fish, shellfish, pigs, and birds
• Pathophysiology: infection usually acquired occupationally by contact with infected meat (enters through abrasions in the hand)
• Clinical features: warm, tender, well-demarcated, erythematous plaques (most commonly affects the hands)
• Treatment: penicillin
• Complications: sepsis, endocarditis

Other

• Dermatological conditions ^[7][18]
  • Acne vulgaris
  • Atopic dermatitis
  • Hidradenitis suppurativa
  • Vascular malformations
• Viral infections
  • HSV infection (e.g., herpetic whitlow, eczema herpeticum)
  • Shingles
• Bacterial infections
  • Lymphogranuloma venereum
  • Cat scratch disease
  • Verruga peruana
  • Botryomycosis
• Fungal infections (e.g., sporotrichosis, kerion)
• Parasitic infections (e.g., scabies, myiasis, larva migrans)

The differential diagnoses listed here are not exhaustive.