OVERVIEW: What every practitioner needs to know

Are you sure of the type of soft tissue infection you are dealing with? What should you expect to find?

Infections of the skin and soft tissues range from mild superficial processes that can be managed in outpatients to life-threatening infections requiring hospitalization, intensive care, and combined surgical and medical support.

Important considerations include:

  • History and epidemiologic factors (exposures to specific pathogens, mechanisms of injury)

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  • Microbiologic factors (virulence and drug susceptibility of invasive pathogens)

  • Host factors (underlying immunosuppression, immunodeficiency, trauma, metabolic disorders, etc.)

The major syndromes of skin and soft tissue infection are generally approached from superficial to deep processes

Infections of the superficial dermis


Impetigo is a superficial skin infection that often begins as a vesicular process which evolves to form crusted and intermittently weeping lesions. Small vesicles typically develop on exposed areas, sometimes associated with a narrow halo of surrounding erythema. The vesicles become pustular in appearance, and readily drain seropurulent material which has a classic golden appearance. The involved areas may be pruritic, and scratching can exacerbate the process with spread to uninvolved areas. Fever and systemic symptoms are uncommon, although regional lymphadenopathy may be present.

Epidemiology: occurs most commonly in children, often after minor trauma (abrasions, insect bites) or complicating primary dermatoses such as eczema. It is more common in warm, humid weather.

Etiology: S. aureus and group A streptococci (S. pyogenes) are the most common causes of impetigo. Non-group A streptococci are occasionally responsible, and group B streptococcal impetigo is usually restricted to newborns.

Differential diagnosis: Primary vesicular herpes group virus infections (varicella, herpes simplex) evolve from vesicular to pustular lesions, but the crusts are firmer without purulent drainage, and the clinical features of rash distribution and systemic findings help to distinguish these processes. It is important to consider secondary impetigo when viral vesicular lesions are slow to heal or have persistent weeping. Pustular psoriasis and acute palmoplantar pustulosis, sterile inflammatory skin disorders, can occasionally mimic impetigo in appearance.

Laboratory features: Swabs of exudate from unroofed vesicles or weeping lesions usually demonstrate gram positive organisms on Gram stain. Culture of this material usually recovers group A streptococci or S. aureus in pure culture or a mixture of these pathogens. Occasionally, non-group A streptococci may be recovered.

Therapy: Limited disease may be treated with topical ointments (mupirocin, retapamulin). Gentle application of topical therapies is important to minimize tissue maceration which can exacerbate the infection. For more extensive disease, empiric oral antibiotic therapy aimed at S. aureus and group A streptococci is typically initiated, and dicloxacillin, amoxicillin/clavulanate, or cephalexin are commonly considered. Initial coverage against methicillin-resistant S. aureus is not routinely required, but MRSA should be considered if there is inadequate improvement with one of these initial empiric therapy choices. Clindamycin or erythromycin may be considered in patients with a history of severe beta-lactam allergy, although the rising incidence of antibiotic resistance reduces the efficacy of such therapy. Patients with severe or extensive disease or beta-lactam allergies should undergo wound culture to guide therapy. (Table I).

Table I.

Antibiotic therapy (by organism) for the treatment of invasive soft tissue infection

Bullous impetigo and staphylococcal scalded skin syndrome

Bullous impetigo occurs primarily in infants and children and is caused by S. aureus strains carrying bacteriophages which express exfoliative toxins. The toxins weaken the adherence of epithelial cells, leading to the formation of vesicles. The vesicles enlarge to form large flaccid bullae containing clear yellow fluid which contain staphylococci on Gram stain and culture. The surrounding skin typically lacks a significant inflammatory halo. Methicillin-sensitive strains of S. aureus respond to the conventional anti-staphylococcal agents noted above. MRSA infections generally respond to oral co-trimoxazole. Widespread disease may be treated with oral linezolid or parenteral vancomycin or linezolid (see below).

Staphylococcal scalded skin syndrome (SSSS) is a more generalized form of bullous impetigo, with widespread Bulla formation and subsequent exfoliation. As with bullous impetigo, this is usually seen in young children. Fever and generalized scarlatina form rash are early signs which progress to the formation of large flaccid bullae. These bullae readily open with minimal friction (Nikolsky sign), and lead to widespread denudation with erythematous, weeping dermis requiring management as a severe second degree burn injury. Unlike limited bullous impetigo, S. aureus is often not recovered from the widely denuded areas, but may be found at the site of an initial soft tissue injury. The major differential diagnostic consideration is toxic epidermal necrolysis, which is an often generalized skin injury process associated with a variety of triggers including drug reactions and rarely systemic infections such as Mycoplasma pneumoniae infection. Skin biopsy or recovery of sloughed bullae (“jelly roll preparation”) distinguish between the intraepidermal cleavage seen with SSSS from the sub-epidermal separation seen with toxic epidermal necrolysis. Parenteral therapy is recommended for SSSS; initial vancomycin therapy to cover possible MRSA is appropriate for this severe illness, with transition to an antistaphylococcal penicillin or cephalosporin if MSSA is isolated.


Folliculitis is caused by bacterial or fungal infection within hair follicles and apocrine glands.

Epidemiology: Folliculitis may develop in otherwise healthy individuals, as well as in a variety of higher risk patients.

Etiology: A wide variety of bacteria and yeasts are associated with folliculitis. S. aureus is the most common etiology, but a variety of Gram-negative bacteria (including P. aeruginosa and A. hydrophila) have been associated with folliculitis after environmental exposures to nonsterile water sources (especially ponds and inadequately chlorinated swimming pools). Fungal folliculitis due to Candida species can occur in infants, particularly in the diaper area, and in other patients (often in intertriginous areas) with heightened risk factors such as obesity, diabetes mellitus, steroid therapy, and prolonged antibiotic use.

Clinical features: Infection of obstructed follicles and glandular ducts lead to characteristic small painful and/or pruritic red papules with central pustule formation and a halo of local desquamation. Facial folliculitis (sycosis barbae) occurs in bearded areas, and pseudomonal folliculitis often develops in relation to bathing suit contact. Candidal folliculitis presents as satellite pruritic papules adjoining areas of cutaneous candidiasis. Folliculitis due to Malassezia furfur occurs particularly in the setting of neutropenia, diabetes mellitus, or corticosteroid administration.

Differential diagnosis: Folliculitis may be confused with acne vulgaris, particularly when localized to facial areas. Fungal folliculitis may mimic disseminated candidiasis, since nodular skin lesions containing yeast forms may be present with disseminated infections. Inflammatory lesions resulting from herpes simplex or scabies infections may mimic folliculitis. Noninfectious dermatoses may have a prominent follicular pattern and resemble infectious folliculitis.

Laboratory features: Laboratory investigation is usually deferred unless there is extensive or refractory disease, or the patient has significant underlying immunodeficiency. Gram stain of an unroofed lesion demonstrates causative bacteria or yeast. Candida species readily grow on routine bacterial media, but M. furfur requires specific fungal media for recovery.

Therapy: Local measures are generally effective at controlling folliculitis. Saline compresses and topical agents (mupirocin for staphylococcal infection, or topical azole antifungal agents such as clotrimazole) are appropriate. Widespread bacterial folliculitis, such as swimming pool folliculitis due to P. aeruginosa, may be treated with a course of oral ciprofloxacin. Further expedited investigation by biopsy is appropriate in the setting of severe or refractory disease.

Complications: Follicular infections can spread beyond the confines of the follicle or apocrine gland and extend into the adjoining subcutaneous tissue, forming a furuncle (see below).

Deeper Dermal Infections

A furuncle or boil is a deeper localized inflammatory process that arises from a folliculitis lesion and extends into the adjoining subcutaneous tissue. Multiple furuncles may coalesce in the subcutaneous fat, creating multiple draining abscesses that are separated in part by bands of connective tissue. These deep, draining, intercommunicating lesions are recognized as carbuncles and are associated with S. aureus infection.

Epidemiology: Furuncles may develop in normal individuals but obese individuals and those with diabetes mellitus, granulocytopenia or functional granulocyte disorders, and/or corticosteroid therapy are generally felt to be at increased risk.

Etiology: The vast majority of furuncles and carbuncles are caused by S. aureus.

Clinical Features: Areas such as the neck, axillae, buttocks, and face are the most common sites of furuncle development, where local trauma (e.g. friction) is common and there are abundant hair follicles and apocrine sweat glands. Furuncles appear as tender, indurated, erythematous nodules that become fluctuant and often drain spontaneously. Carbuncles are deeper, and are most commonly found at the neck, back, and thighs and are accompanied by systemic symptoms such as fever and malaise, reflecting the greater extent of infection. Lesions may drain spontaneously but may also lead to deeper infection with the development of bacteremia and the risk of metastatic staphylococcal infection to vascular or skeletal sites. Facial lesions, especially if manipulated, may spread to the cavernous sinus through the facial venous structures.

Differential diagnosis: Furuncles and carbuncles are almost always the result of S. aureus infection, and have been seen with both MSSA and MRSA isolates. Unusual organisms associated with occupational or recreational exposures may sometimes be responsible, including nontuberculous mycobacteria. Hidradenitis suppurativa is often mistaken for primary pustular infection, but its restricted location to the axillae, groin, buttock cleft, or rarely the areolae distinguish this process from furuncles and carbuncles. In addition, cultures of hidradenitis lesions often recover mixed flora, rather than a pure culture of S. aureus. The lesions of cutaneous myiasis (botfly larval infestation (Dermatobium hominis)) mimic furuncles but have a central pore which is the source of air for the botfly maggot and on occasion this larval form is visible in the central pore.

Laboratory features: S. aureus is generally recovered from draining furuncles, but limited disease in otherwise normal hosts is not always subjected to Gram stain and culture of purulent material. Immunocompromised patients, and those who have recently received antibiotics or have been hospitalized, are at increased risk of MRSA infection, and should have culture performed. Individuals with extensive carbuncles should be routinely cultured if possible, and biopsy for histology and full cultures should be considered in patients who fail conventional therapy.

Therapy: Local measures, including the application of warm compresses, often successfully promote the localization and eventual drainage of furuncular lesions. Antibiotic therapy is indicated for patients with surrounding cellulitis, severe or extensive disease, carbuncle formation, and those with underlying host problems as noted above. As with other forms of staphylococcal infection, mild and moderate cases may be treated empirically with conventional antistaphylococcal agents, but patients with more severe disease or epidemiologic risk factors for MRSA infection should receive primary therapy effective against MRSA. Surgical drainage should be performed for larger and extensive lesions, and initial parenteral therapy with IV vancomycin or other agents effective against MRSA and MSSA such as linezolid or daptomycin.

When patients develop recurrent furunculosis, efforts to reduce skin trauma and staphylococcal carriage and improve overall hygiene are appropriate. Daily chlorhexidine scrubs followed by a gradually reduced frequency and avoidance of autoinoculation through patient manipulation of lesions are important measures; assessment of staphylococcal nasal carriage and consideration of nasal mupirocin administration (twice daily for 5 days using mupirocin nasal ointment) for nasal carriers is appropriate. Combined topical and systemic antibiotic therapy using rifampin and doxycycline may be considered in occasional patients with ongoing recurrent disease.


Ecthyma is a localized ulcerating dermal infection that is generally associated with group A streptococcal infection.

Epidemiology: Ecthyma lesions are common in children but may occur in individuals of all ages. A primary inciting event (insect bite, excoriation, abrasion) is common but these lesions may develop without a recognized local injury. In closed populations (e.g., military recruits) epidemic spread of ecthyma can occur.

Etiology: Group A streptococci typically are the primary pathogen responsible for the development of ecthyma. S. aureus may be recovered from the lesions in addition to Group A streptococci, but are generally a secondary invader of the ulcerating process.

Clinical features: Ecthyma lesions typically begin as a localized area of impetigo, but progress to the dermis to produce a local “punched out” ulcer with overlying purulent crusts and a raised, violaceous border. Systemic spread of infection is very rare.

Differential diagnosis: Unlike the relatively indolent course of streptococcal ecthyma, the lesions of ecthyma gangrenosum may begin as punched out ulcers with surrounding violaceous inflammation but progress rapidly to a life-threatening infection. Ecthyma gangrenosum is associated primarily with P. aeruginosa infection (although other Gram – negative pathogens are occasionally responsible). The lesions generally develop in immunocompromised hosts, undergo rather rapid expansion and destruction of surrounding tissue, and are associated with rapidly progressing systemic toxicity which may progress to septic shock. Orf, localized ulcerating lesions caused by a poxvirus associated with ruminant livestock (especially sheep and goats), may develop in individuals who have close contact with these animals. The lesions develop most commonly on the hands and not surprisingly fail to respond to anti-streptococcal antibiotic therapy.

Laboratory features: Limited ecthyma lesions are often initially treated empirically without laboratory investigation. Severe, extensive, or persistent lesions failing to improve with initial antibiotic therapy targeted against group A streptococci and S. aureus should be cultured to assess possible superinfection by S. aureus, with particular concern regarding MRSA.

Therapy: Mild and limited disease may be treated with topical mupirocin or retapamulin. Oral systemic therapy is often administered in conjunction with topical therapy or in sequential fashion if the lesions fail to recede with topical therapy alone. Patients with large or multiple lesions should receive initial systemic therapy in addition to topical agents. Initial oral therapy may be directed against Group A streptococci and S. aureus (cephalexin, dicloxacillin, clindamycin) but in some instances MRSA may be present and require targeted therapy, based on the sensitivities of the MRSA isolate (co-trimoxazole, clindamycin, etc.) agents.


Erysipelas is a distinctive rapidly spreading infection of the dermis (cellulitis) caused almost always associated with Group A streptococcal infection.

Epidemiology: Erysipelas may develop in patients across the age spectrum, particularly among infants and children and among the elderly. Infection may develop in areas where the skin barrier has been disrupted by trauma or primary skin lesions such as eczema or psoriasis, but may arise in areas of apparently normal skin. Infection is thought to spread through lymphatic channels in the dermis, so individuals with postoperative and/or post-irradiation lymphatic obstruction (especially post-mastectomy, lymph node dissection, etc.) are at highest risk. Lymphatic scarring from initial bouts of erysipelas may predispose to recurrent episodes. Individuals with any of a variety of disorders associated with lymphatic and/or venous obstruction (lymphedema, nephrotic syndrome, venous stasis, obesity) as well as metabolic disorders such as diabetes mellitus and alcohol abuse have increased risks as well.

Etiology: Erysipelas is caused primarily by Group A streptococci, but has been associated with other streptococcal serotypes in normal hosts. Together, staphylococci and gram negative bacilli have been recovered from blood cultures in nearly one-quarter of those patients with documented bacteremia. Unfortunately, a specific bacterial pathogen is identifiable through blood cultures in only a small subset of cases (<5% of blood cultures).

Clinical features: An enlarging painful and sharply demarcated, raised, indurated, erythematous lesion is the hallmark of erysipelas, and is accompanied by fever and systemic toxicity. The edematous skin often has a “peau d’orange” appearance, and in extreme cases may form fluid-filled bullae. The malar areas are classically involved, with bilateral infection spreading across the nasal bridge, but infection may occur anywhere on the body, with a relative predilection for the lower extremities.

Differential diagnosis: The rapidly expanding and painful nature of erysipelas lesions, frequently accompanied by fever, is quite distinctive. Cellulitis involves the subcutaneous layer and has less well-defined borders. The erythema chronicum migrans lesion of early Lyme disease is not as painful as erysipelas, expands more slowly, and classically has central clearing (“bull’s eye lesion”). Erysipeloid is a more indolent infectious process typically involving the extremities following occupational or recreational contact with seafood, salt water fish, or a variety of farm animals. Rarely, erythematous plaques may develop in the course of bacteremic infections in immunocompromised hosts. A variety of noninfectious lesions including contact dermatitis, localized urticaria, cutaneous lesions in Familial Mediterranean fever, and inflammatory breast carcinoma may superficially mimic erysipelas but their clinical setting, tempo, and associated symptoms are distinct.

Laboratory features: The skin almost always remains intact despite eryspelas and surface cultures are unrevealing; blood cultures are positive for Group A streptococci or other pathogens only occasionally. Group B streptococci can rarely cause erysipelas in neonates, and non-Group A streptococci, S. aureus or gram-negative bacilli may occasionally associated with an erysipelas-like rash.

Therapy: Early stage (mild) erysipelas in otherwise healthy individuals may be treated with oral penicillin or other oral agents effective against Group A streptococci. The incidence of macrolide resistance has been growing and its use should be monitored carefully when given to patients allergic to beta lactam agents. Most patients require parenteral penicillin therapy until there is clear improvement. In patients in whom it is more difficult to distinguish erysipelas from deeper cellulitis, coverage with an antistaphylococcal beta lactam (nafcillin, oxacillin, or a first generation cephalosporin) should be considered. In compromised hosts, coverage with an antistaphylococcal agent as well as effective broad spectrum gram negative coverage (e.g., vancomycin and ciprofloxacin or cefepime) should be considered.

Prevention: Long-term suppressive therapy with oral penicillin (e.g., penicillin VK 250 mg twice daily) has been suggested to reduce the incidence of recurrent erysipelas. This should be reserved for patients with demonstrated repeated bouts of erysipelas or cellulitis in a single body site.

Infections primarily involving subcutaneous tissue


Cellulitis reflects deeper cutaneous infection than that seen with erysipelas, with involvement of the dermis as well as the deeper subcutaneous structures. As a result, the dermal erythema and edema may be less well-demarcated.

Epidemiology: Cellulitis may occur in individuals of any age. Local trauma or underlying skin disorders including dermatophyte infection of the distal lower extremities provide a portal of local entry for skin bacteria (most commonly Group A or non-group A streptococci, less commonly S. aureus, or a variety of other pathogens with distinct epidemiologic risk factors). The initial skin injury may be prominent (major trauma, surgery, laceration) or seemingly trivial (minor abrasions, athletic trauma, shaving). Occasionally cellulitis may complicate primary bacteremia or a primary deep soft tissue infection (abscess, draining fistulae, etc.).

Additional risk factors for the development of cellulitis are similar to those leading to erysipelas. Lymphatic stasis due to primary lymphedema, congenital anomalies of the lower extremity, or surgery involving the lymphatics may increase the risk of cellulitis. A variety of surgical procedures have been particularly associated with cellulitis, including saphenous vein harvesting for coronary artery bypass grafting, mastectomy or lumpectomy and axillary dissection, pelvic procedures including radical pelvic surgery with pelvic and/or inguinal node dissection, pelvic irradiation, etc. Less invasive procedures such as liposuction, body piercing, and injection drug use may also increase the risk of post-procedure cellulitis.

Etiology: Most episodes of cellulitis are caused by group A and non-group A streptococci. When S. aureus is the cause of a cellulitic process, a small central purulent focus or even a deeper subcutaneous abscess may be present. A variety of other pathogens cause cellulitis in distinct clinical settings. (Table II) (Table III).

Table II.

Cellulitis syndromes with particular anatomic foci in normal hosts

Table III.

Cellulitis syndromes associated with particular environmental exposures

Clinical features: Local erythema and edema associated with tenderness and pain develop, generally at a site of inciting trauma or skin injury. The portal of entry may be removed from the cellulitic area if the causative pathogen spreads via draining lymphatics before establishing infection (as when toe dermatophyte infection with fissuring of the interdigital web spaces leads to pretibial cellulitis). The cellulitic area expands in size, and the local symptoms progress in severity. Fever, malaise, and rigors are common as the area of cellulitis evolves. Streptococcal cellulitis generally progresses more rapidly than staphylococcal infections. The margins of the infection are poorly demarcated and often quite irregular, sometimes with areas of normal skin (“skip areas”) surrounded by infection. Regional lymph nodes may enlarge with marked local tenderness. Erythematous lymphangitic streaking proximal to the area of infection may be seen. Bullae may develop in the areas of most intense skin edema and slough, leaving a weeping erythematous dermal base which may become secondarily infected. Bacteremia is common in patients with extensive or severe disease, especially when fever and rigors are present.

There are several cellulitis syndromes associated with specific pathogens and/or body sites: (Table II) (Table III) (Table IV)

Table IV.

Cellulitis syndromes in immunocompromised hosts

Differential diagnosis: Most diagnostic uncertainty relates to the specific bacterial pathogens responsible for an episode of cellulitis and the appropriate initial empiric antibiotic therapy required (see below). It is crucial to distinguish among several deeper soft tissue infections such as necrotizing fasciitis and anerobic myonecrosis, since these processes require urgent surgical debridement. Noninfectious cellulitis-like rashes have been seen in the setting of common sterile inflammatory disorders such as insect bites, drug eruptions, gout or deep venous thrombophlebitis, and rare processes such as Sweet’s syndrome, Well’s syndrome, Kawasaki Disease, and Familial Mediterranean Fever.

Laboratory Features: Confirmation of a specific bacterial cause is successful in only a small minority of cases, generally based on blood culture isolates. Aspiration of the edge of the cellulitic process has a similarly low yield and is generally deferred unless unusual pathogens are suspected based on environmental considerations or host immunodeficiency. Bullae, if present, may be aspirated for fluid Gram stain and culture. When cellulitis complicates an ischemic or diabetic ulcer, multiple potential pathogens are readily recovered from swab or biopsy cultures of the ulcer base, but the precise role of each pathogen regarding the adjoining cellulitis is not entirely clear. Leukoytosis on routine hematology testing is the rule. Imaging of cellulitic areas is generally not required, but plain films may identify a radioopaque foreign body in posttraumatic infections or rarely a subperiosteal abscess or chronic osteomyelitis presenting with cellulitis. Cross sectional imaging (e.g., MRI) is occasionally necessary to assess the depth of infection when severe bullous cellulitis is present regarding the possible need for surgical exploration due to concern for necrotizing deep soft tissue infection.

Therapy: Empiric therapy is routinely targeted against hemolytic streptococci and S. aureus. Mild cases may be treated with oral penicillinase-resistant agents such as dicloxacillin (1.5- 2 grams daily) or a first generation cephalosporin such as cephalexin. In uncomplicated cellulitis of the extremities oral antibiotics have been shown to be as efficacious as parenteral therapy. A delayed response to therapy most commonly reflects underlying conditions. Female sex, cardiovascular disease, higher body mass index, shorter duration of symptoms, and cellulitis other than typical erysipelas predict nonresponse at day 3, and less commonly reflect infection with a resistant pathogen or failure of oral therapy. However, patients with specific risk factors, such as athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, those with prior MRSA exposure, and intravenous drug users should be covered for MRSA. Oral MRSA coverage with co-trimoxazole at moderately high dose (320 mg trimethoprim component twice daily) or parenteral therapy with vancomycin should be initiated. When a detailed exposure history suggests exposure to other possible pathogens, targeted therapy against the suspect agents should be added to routine coverage (Table I). Patients with anatomic abnormalities (postoperative, lymphatic obstruction, etc.) often respond very slowly despite appropriate treatment, and may require prolonged parenteral therapy.

Gangrenous (necrotizing) cellulitis

Gangrenous cellulitis is a severe and rapidly progressive infection of the skin and subcutaneous soft tissue that results in necrosis of the overlying skin and subcutaneous tissues. Several processes, each with distinctive clinical features and microbiologic findings, may cause gangrenous cellulits: (Table V).

Table V.

Gangrenous (necrotizing) cellulitis

Epidemiology: These severe and life-threatening infections are rather rare. Early recognition of these processes is critical, since urgent surgical exploration and debridement of necrotic tissue is the cornerstone of successful therapy. As noted above, streptococcal gangrene usually complicates penetrating injuries of the extremities, although primary skin lesions (e.g., varicella) can be a predisposing factor. On rare occasions no portal of entry is apparent. Similarly, gangrenous cellulitis complicating polymicrobial necrotizing fasciitis is most commonly a post-traumatic or post-surgical process. Progressive bacterial synergistic gangrene develops following abdominal surgery, particularly after bowel resection or stoma creation; this can develop as a complication of chronic extremity ulcers as well. Synergistic necrotizing cellulitis often develops on the abdominal wall, perineum, or proximal lower extremities in diabetic individuals without a clear cut precipitating event.

Clinical features: Gangrenous cellulitis may develop with or without complicating necrotizing fasciitis. Types I and II necrotizing fasciitis are defined by their polymicrobial or streptococcal etiology, but otherwise are often quite similar in appearance and striking rapidly progressive courses. Initial severe local pain and erythema worsen, with rapidly enlarging borders and evolution from erythema to a dusky appearance with the formation of bullae filled with yellow, hemorrhagic or even dark fluid. The features of streptococcal toxic shock may accompany streptococcal necrotizing cellulitis, and bacteremia with metastatic infections is common. The areas of involved skin will develop frank necrosis and may ulcerate and slough. Clostridial anerobic cellulitis has a less fulminant course and is associated with less systemic toxicity. It is notable for the presence of frank crepitus in the region of infection, and the drainage of foul-smelling fluid. Progressive bacterial synergistic gangrene evolves from a routine postoperative wound infection to a progressive painful, ulcerating lesion surrounded by a halo of gangrene.

Differential diagnosis: An initial assessment must be made regarding the extent and depth of infection and need for urgent surgical exploration. The presence of pain disproportionate to the skin findings and the development of bullae complicating severe cellulitis are warning signs of deep disease and need for surgery. Once confluent areas of necrotic skin develop, the diagnosis becomes clear but late diagnosis is associated with increased risk of death and the need for very extensive, disfiguring debridement. In the absence of crepitus, specific diagnosis depends on Gram stain and culture of bulla fluid and intraoperative cultures of debrided material. The dramatic nature of these infections is not readily confused with other processes. Frank necrotizing fasciitis must be considered to avoid inadequate surgical debridement. Progressive bacterial synergistic gangrene lesions may be mimicked by postoperative Entameba histolytica infection, and can be assessed by skin biopsy, scrapings, stool examination and serology in appropriate cases. Necrotizing spider bites (e.g. the brown recluse spider) may produce necrotizing skin lesions that mimic gangrenous cellulitis. Late-presenting third-degree burn wounds also may resemble necrotizing cellulitis, with skin necrosis, large bulla formation, systemic toxicity and hypotension, but the relevant history distinguishes these processes. Skin and subcutaneous fat necrosis due to calcific uremic arteriopathy (calciphylaxis) may be seen in patients with chronic renal failure.

Laboratory features: Gram stain and cultures of bulla fluid often reveal the etiologic agents. Blood cultures are helpful, particularly in the setting of suspected necrotizing fasciitis. Leukocytosis is common, although leukopenia may be present with severe disease. The laboratory derangements of streptococcal toxic shock accompany the clinical findings of toxic shock in patients with streptococcal necrotizing cellulitis (coagulopathy, renal insufficiency, hepatitis, thrombocytopenia, etc). Plain films will demonstrate abundant soft tissue gas in a pattern that is more superficial than that seen with clostridial myonecrosis. Biopsy for histologic analysis and culture is critical for immunocompromised patients with necrotizing cellulitis, where there is a broad differential diagnosis of causative agents and frequent difficulty recovering fungi from bulla fluid or other superficial cultures, and urgency in initiating proper empiric therapy.

Therapy: Resuscitative efforts with fluid and pressors when necessary, together with empiric antibiotic coverage and prompt surgical debridement are the mainstays of treatment of necrotizing cellulitis. The affected area should be opened widely with debridement of all necrotic tissue and drainage, irrigation of purulent material, and thorough inspection of the deep fascia and muscle layers to exclude possible necrotizing fasciitis and/or myonecrosis. Antibiotic therapy, while important, is unable to gain control of these infections due to tissue necrosis with loss of blood flow and delivery of granulocytes, humoral proteins, and antibiotics.

Empiric antibiotic recommendations are listed below. High dose intravenous antibiotic regimens are utilized to cover streptococci (both hemolytic and microaerophilic/anerobic species), gram negative bacilli (particularly Enterobacteriaceae), and anerobic species including Clostridia and Bacteroides. In immunocompromised hosts, empiric coverage of Pseudomonas should be included as well. Use of vancomycin for possible staphylococcal infection and a beta lactam/beta lactmase inhibitor combination such as piperacillin/tazobactam or a penem agent such as imipenem or meropenem are appropriate initial therapies prior to Gram stain assessment. In the presence of hypotension and possible toxic shock, intravenous clindamycin should be added to suppress possible toxin production, and administration of high dose IVIG to bind circulating toxin may be considered. Reexploration at 24-48 hours for possible additional debridement of any residual necrotic tissue is important.

Necrotizing fasciitis

Necrotizing fasciitis, like gangrenous (necrotizing) cellulitis, is uncommon. It is characterized by infection extending to the superficial (and often to the deep) fascial layers, with a rapid and progressive course, marked toxicity, and the absolute need for surgical exploration as part of comprehensive management.

Epidemiology: Necrotizing fasciitis develops following superficial or penetrating injury (trauma, lacerations, insect bites, abrasions, burns) and surgery, particularly involving the abdominal cavity or perineum. Intestinal injury due to trauma, diverticulosis, neoplasm, or penetrating foreign body are important causes. Individuals with diabetes mellitus, alcoholism, and injection drug use are thought to be at increased risk. Rarely, neonates with omphalitis may develop necrotizing fasciitis.

Clinical features: Necrotizing fasciitis most commonly develops on the lower extremities, but the abdominal wall and perineum may be involved following abdominal trauma or surgery. Surgical wounds at any site may develop this complication as well. The process begins as local cellulitis, with erythema, edema, pain, and marked tenderness. Like more superficial cellulitidies, the margins of infection are poorly defined. Necrotizing fasciitis may develop in the extremities in relation to peripheral vascular insufficiency. Diabetic males may develop necrotizing fasciitis initially involving the male genitalia with extension to the perineum and abdominal wall, often following urologic or anorectal procedures or local infection. Extreme pain and systemic toxicity disproportionate to the clinical findings at presentation are common, and severe pain increases the likelihood of necrotizing fasciitis versus cellulitis.

The infection progresses over the course of one or a few days, despite antibiotic therapy, with gradual skin discoloration from initial erythema to areas of frank necrosis. Bullae containing hemorrhagic fluid develop at the affected areas. In contrast to other deep infections, sensation in the involved areas is often lost due to local microvascular and nerve injury. The soft tissue edema may be quite dramatic, and when involving the extremities raises concern for a possible compartment syndrome with risk of secondary myonecrosis. Gas formation is often present in the presence of mixed infection containing anerobic or microaerophilic species, especially in diabetic patients. High fever and clinical toxicity are common.

Differential diagnosis: Necrotizing fasciitis shares many features with deep cellulitic processes, particularly gangrenous cellulitis. A history of diabetes mellitus and/or antecedent local trauma are common in all of these processes. In essentially all patients with features concerning for necrotizing fasciitis, surgical exploration and debridement is key to remove necrotic tissue and purulent material and to establish a definitive microbiologic process. On occasion air is entrapped in the soft tissues as the result of a penetrating injury or vigorous wound irrigation, or dissection from a tracheostomy or other device. In these situations, crepitus develops immediately after the inciting event, and there are no signs of local infection accompanying the crepitus.

Laboratory features: Leukocytosis is generally present and a CRP increase of 5 fold or greater suggests this diagnosis rather than cellulitis. Sepsis is commonly associated with acute renal insufficiency and hyponatremia. Gram stains of the exudative fluid demonstrate the causative agents. Mixed infection is common, except in pure streptococcal necrotizing fasciitis, where only chains of Gram positive cocci may be observed. Blood cultures are often positive and should be obtained prior to the initiation of antibiotics, if possible. Surgery should not be unduly delayed for imaging studies. When readily available, ultrasound generally detects the presence of tissue gas which is particularly helpful in distinguishing these processes from severe cellulitis. If readily available, CT or MRI will demonstrate subcutaneous and facial edema, the presence of gas in the tissues, and hypoperfused or necrotic tissue. Cross-sectional imaging is particularly helpful when evaluating relatively inaccessible regions such as the retroperitoneum, and in anatomically complex areas such as the neck, upper chest, and mediastinum. At surgery, tissue for frozen section analysis and gram stain help guide initial management.

Therapy: The high mortality rate of the necrotizing fasciitis syndromes can be reduced to ~10-15% by prompt diagnosis and aggressive comprehensive management. Prompt surgical exploration for patients with typical findings of necrotizing fasciitis, with severe local edema, skin necrosis, hemorrhagic bullae +/- clinically apparent crepitus and severe toxicity, is critical. Initial broad spectrum antibiotic coverage is appropriate en route to surgical exploration. Preferred empiric regimens include ampicillin, gentamicin, and metronidazole; ampicillin-sulbactam or piperacillin-tazobactam and gentamicin; or a penem agent such as imipenem or meropenem, often with gentamicin. Gentamicin use should be individualized, balancing toxicity and potential efficacy. It may be omitted or restricted to a single dose in the presence of significant azotemia or ongoing hemodynamic instability. Gentamicin is more important when ampicillin is part of the initial regimen than when broader spectrum initial therapies are considered. Clindamycin is often added when streptococcal necrotizing fasciitis and associated toxic shock is suspected in order to suppress toxin production. When streptococcal necrotizing fasciitis is present, therapy may be narrowed to penicillin or ampicillin together with clindamycin. The treatment of the polymicrobial processes usually requires ongoing broad-spectrum therapy, particularly when tissue cultures were obtained in the operating room after the patient received initial empiric therapy.