Necrotizing Soft Tissue Infections - Complicated Skin Infections

Indications for Testing

Appropriate clinical presentation in addition to a high level of suspicion for the disease

Laboratory Testing

Simple infections
- Gram stain of aspirates or tissue biopsies – may not be as helpful as culture, depending on organism involved and quality of specimen
- Cultures of tissue, wound

More complicated infections (fever, tachycardia, immunocompromised patients)

CBC – elevated white cell count >15,000/mm³ with neutrophil predominance (left shift) frequently noted
Cultures of tissue, wound crucial
Blood cultures – infrequently positive but helpful for organism identification
C-reactive protein
Use of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score – ≥6 points has positive predictive value of 92% and negative predictive value of 96% for necrotizing fasciitis

Laboratory Risk Indicator for Necrotizing Fasciitis

Laboratory Risk Indicator for Necrotizing Fasciitis
Variable, Units	Score
C-reactive protein, mg/L
<150	0
≥150	4
Total white cell count, per mm³
<15	0
15-25	1
>25	2
Hemoglobin, g/dL
>13.5	0
11-13.5	1
<11	2
Sodium, mmol/L
≥135	0
<135	2
Creatinine, µmol/L
≤141	0
>141	2
Glucose, mmol/L
≤10	0
>10	1
Maximum score is 13. A score of ≥6 should raise the suspicion of necrotizing fasciitis. A score of ≥8 is strongly predictive of this disease.

If above studies do not confirm necrotizing fasciitis, surgical exploration of the site may confirm the disease

Imaging Studies

X-ray – subcutaneous air in tissue noted in about 25% of patients
- May reveal foreign body in infected wounds
US/CT/MRI – choose imaging study based on suspected location of infection and usefulness of study for site infected
- Imaging frequently used for localized drainage of identified site

Differential Diagnosis

Local infections (furuncles, cellulitis, abscesses, etc.)
Insect and spider bites
Fungal (Candida) septicemia
Allergic reaction
Crystalline arthritis
Tenosynovitis (associated with inflammatory arthropathy)

Aggressive soft tissue infections can cause extensive local tissue damage as well as systemic toxicity. These infections require prompt recognition in order to prevent severe morbidity and mortality.

Epidemiology

Incidence – 4/100,000
Age – usually occurs in older patients
Sex – M:F, equal
- Exception in Vibrio vulnificus, M>F
Transmission – skin entry via break in dermis (usual route)

Classification

Gangrene
Necrotizing fasciitis/cellulitis
Myositis/myonecrosis
Complicated/deep abscesses
Infected burns/surgical wounds
Toxin-mediated – toxic shock syndrome, staphylococcal scalded skin syndrome

Organisms

Single organism common in uncomplicated infections; polymicrobic/synergistic more prominent in complicated infections
- Staphylococcus spp (including methicillin-resistant Staphylococcus aureus[MRSA]), enterococci, Pseudomonas aeruginosa, Streptococcus spp, Enterobacteriaceae, Bacteroides spp, Proteus spp, Clostridium spp
  - Most common – Staphylococcus aureus, Streptococcus spp
- Aerobic and anaerobic organisms frequently found in combination

Risk Factors

Diabetes mellitus
Alcoholism
Immunocompromised state
Liver disease
Peripheral vascular disease
Obesity
Trauma
Burns
Age >50 years

Clinical Presentation

General symptoms
- Skin – erythema, tense edema, vesicles or bullae, necrosis ulcers, crepitus, gray or discolored wound drainage, pain extending past margin of skin infection
- Constitutional – fever, diaphoresis, delirium, tachycardia, tachypnea
- Most common locations – extremities (50-55%), perineum/buttocks (20%), trunk (18-20%), head and neck (8-10%)
Clinical markers that may help differentiate necrotizing infection from localized infection include the following
- Pain disproportionate to appearance of infection
- Crepitus
- High fever
- Rapidly spreading erythema

Organisms and clinical scenarios/presentations

Organism	Common Clinical Scenario	Most Common Underlying Comorbid Illnesses	Clinical Presentation	Prevalence
Group A Streptococcus species	Skin abrasion, trauma, recent skin infection (herpes zoster, varicella-zoster, herpes simplex), human bite, intravenous/ subcutaneous drug abuse	Diabetes, cancer, alcoholism, stasis dermatitis, eczema	Intense erythema, edema and pain, lymphadenopathy, hemorrhagic and necrotic bullae, muscle myositis, erysipelas, impetigo; type II necrotizing fasciitis	One of the two most common monomicrobial infectious agents
Peptostreptococcus and gram-negative	Colorectal or genitourinary disease; orofacial surgery, dental work	Older patients	Scrotal edema and perineal gangrene (Fournier gangrene), submandibular space (Ludwig angina)	Usually found in association with other organisms
Staphylococcus aureus	Skin trauma, recent hospitalization or surgery, intravenous/ subcutaneous drug abuse	Obesity, diabetes, immunocompromising condition, eczema, rheumatologic diseases	Furuncles, local abscesses, diffuse macular erythroderma, pyomyositis, toxic shock syndrome, staphylococcal scalded skin syndrome	One of the most common agents of soft tissue skin infections
Polymicrobial – often beta hemolytic streptococci with S. aureus (including MRSA), S. epidermidis or gram-negative bacteria such as E. coli, Proteus mirabilis, Klebsiella pneumoniae	Diabetic foot ulcer, recent surgery with purulent wound	Diabetes, immunocompromising condition, vascular disease (particularly lower extremity disease)	Moist gangrene with a foul odor, suppurative-necrotic ulcer surrounded by concentric zones of red cellulitis (Meleney gangrene), deeper abscess, type I necrotizing fasciitis	Most common presentation (>50% of all necrotizing soft tissue infections)
Pseudomonas species	Bacteremia, moist skin infection, severe burn, recent hospitalization	Immunocompromising condition, diabetes	Hemorrhagic and necrotic bullae
Vibrio vulnificus	Exposure to raw or undercooked seafood or exposure to seawater	Underlying liver disease, immunocompromising condition	Hemorrhagic and necrotic bullae, ecchymoses	Unusual in immunocompetent patients
Clostridium perfringens	Severe trauma with wound contamination, recent surgery, intravenous drug abuse	None	Pale skin, edema, hemorrhagic and necrotic bullae, foul-smelling discharge, gas formation	Usually found in association with local tissue injury
Pasteurella multocida	Cat or dog bite	None	Erythema, edema, serosanguineous discharge, lymphadenitis, tenosynovitis	Typically associated with animal bite
Aspergillus, Mucor, Rhizopus	Traumatic wounds or burns	Immunocompromising condition	Erythema, severe pain, hemorrhagic bullae	Rarely occurs in immunocompetent patients
Aeromonas hydrophila	Exposure to fresh water, skin abrasion	Usually none; sometimes an immunocompromising condition	Erythema, bullae, necrosis, possible gas formation	Unusual in immunocompetent patients

Treatment

Initiate antibiotic therapy appropriate for polymicrobial infections; change therapy to match culture results
Aggressive wound care, including wide-area surgical debridement
- Necrotizing wounds are commonly fatal if not treated within 72 hours

Prevention

Vibrio – do not eat raw seafood; avoid exposing open wounds to seawater
Pasteurella – prophylaxis started at time of bite for serious bite wounds

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Help differentiate aggressive (systemic) infection from local infection

Limitations:

May not be elevated in spite of aggressive disease

Test name: Wound Culture (Includes Gram Stain 0060101)

ARUP #: 0060132

Methodology: Standard reference procedures for bacterial stain, aerobic culture, and identification. Anaerobe Culture is performed on properly collected specimens (Anaerobe culture 0060143).

Use:

Identify organism causing infection

Test name: Blood Culture

ARUP #: 0060102

Methodology: Continuous Monitoring Blood Culture/Identification

Use:

May be useful in patients with toxic appearance/presentation

Limitations:

Testing is limited to the University of Utah Health Sciences Center only

Test name: C-Reactive Protein

ARUP #: 0050180

Methodology: Quantitative Immunoturbidimetric

Use:

Component of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score

Test name: Electrolytes, Urine

ARUP #: 0020498

Methodology: Quantitative Ion-Selective Electrode

Use:

Component of LRINEC score

Test name: Glucose, Plasma or Serum

ARUP #: 0020024

Methodology: Quantitative Enzymatic

Use:

Component of LRINEC score

Additional Tests Available

Test name: Clostridium botulinum culture

ARUP #:

Methodology:

Comments:

ARUP recommends contacting your local or state health department in suspected botulism cases

If local and state officials are not available, the CDC can be contacted at (404) 639-2206, Monday through Friday, 8:00 a.m. - 4:30 p.m. Eastern time or at (404) 639-2888 at other times; in California, contact CHDS at (510) 540-2308

General

Fisher, Mark A., PhD. Medical Director, Bacteriology and Antimicrobials at ARUP Laboratories; Assistant Professor of Pathology, University of Utah

Comprehensive Review: September 2011
Last Update: September 2011

Actinomyces and Nocardia Species

Clostridium tetani

Staphylococcal Disease

Streptococcal Disease, Group A

Streptococcal Disease, Group B