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Necrotizing soft tissue infections

Necrotizing soft tissue infections
Authors:
Dennis L Stevens, MD, PhD
Larry M Baddour, MD, FIDSA, FAHA
Section Editors:
Michael R Wessels, MD
Morven S Edwards, MD
Deputy Editor:
Elinor L Baron, MD, DTMH
Literature review current through: Aug 2021. | This topic last updated: Aug 25, 2021.

INTRODUCTION — Necrotizing soft tissue infections (NSTIs) include necrotizing forms of fasciitis, myositis, and cellulitis [1-3]. These infections are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality. Accurate diagnosis and appropriate treatment must include early surgical intervention and antibiotic therapy.

Several different names have been used to describe the various forms of necrotizing infections; this is related in part to naming based on clinical features rather than surgical or pathologic findings. The degree of suspicion should be high since the clinical presentation is variable and prompt intervention is critical. The lay press has referred to organisms that cause NSTI as "flesh-eating bacteria."

Necrotizing fasciitis, myositis, and cellulitis will be reviewed here. Clostridial infection and pyomyositis are discussed separately. (See "Clostridial myonecrosis" and "Pyomyositis".)

Surgical management of NSTI is discussed separately. (See "Surgical management of necrotizing soft tissue infections".)

CONDITIONS, MICROBIOLOGY, AND EPIDEMIOLOGY — NSTI can include involvement of the epidermis, dermis, subcutaneous tissue, fascia, and muscle [1]. Necrotizing infection may be categorized based on microbiology and presence or absence of gas in the tissues (table 1).

Distinguishing necrotizing fasciitis from necrotizing myositis may be difficult as skeletal muscle and fascia are involved in both syndromes [4-6]. Necrotizing myositis primarily involves skeletal muscle, whereas necrotizing fasciitis primarily involves fascia.

Necrotizing fasciitis — Necrotizing fasciitis is an infection of the deep soft tissues that results in progressive destruction of the muscle fascia and overlying subcutaneous fat. Infection typically spreads along the muscle fascia due to its relatively poor blood supply; muscle tissue is frequently spared because of its generous blood supply [7]. Development of anesthesia may precede the appearance of skin necrosis and provide a clue to the presence of necrotizing fasciitis [8]. Initially, the overlying tissue can appear unaffected; therefore, necrotizing fasciitis is difficult to diagnose without direct visualization of the fascia.

Necrotizing fasciitis may be divided into two microbiologic categories: polymicrobial (type I) and monomicrobial infection (type II) [9-11]:

Polymicrobial (type I) necrotizing infection is caused by aerobic and anaerobic bacteria.

Typically, at least one anaerobic species (most commonly Bacteroides, Clostridium, or Peptostreptococcus) is isolated in combination with Enterobacteriaceae (eg, Escherichia coli, Enterobacter, Klebsiella, Proteus) and one or more facultative anaerobic streptococci (other than group A Streptococcus [GAS]) [12-14]. Obligate aerobes (such as Pseudomonas aeruginosa) are rarely components of such mixed infections. Uncommonly, fungi (predominately Candida species) are recovered in polymicrobial (type I) necrotizing infection [15].

Fournier gangrene is caused by facultative organisms (E. coli, Klebsiella, enterococci) along with anaerobes (Bacteroides, Fusobacterium, Clostridium, anaerobic or microaerophilic streptococci) [16]. (See 'Involved sites' below.)

Necrotizing infection of the head and neck is usually caused by mouth anaerobes (such as Fusobacteria, anaerobic streptococci, Bacteroides, and spirochetes). (See 'Involved sites' below.)

Other terms for polymicrobial (type I) infection include synergistic necrotizing cellulitis and progressive bacterial synergistic gangrene.

Monomicrobial (type II) necrotizing infection is usually caused by GAS or other beta-hemolytic streptococci. Infection may also occur as a result of Staphylococcus aureus [17,18]. Infection with no clear portal of entry occurs in about half of cases; in such circumstances, the pathogenesis of infection likely consists of hematogenous translocation of GAS from the throat (asymptomatic or symptomatic pharyngitis) to a site of blunt trauma or muscle strain [1,6].

M protein is an important virulence determinant of GAS. Necrotizing infection caused by GAS strains with M types 1 and 3 is associated with streptococcal toxic shock syndrome in about 50 percent of cases [19-21]. GAS strains of these and other serotypes can produce pyrogenic exotoxins, which induce cytokine production, likely contributing to shock, tissue destruction, and organ failure [5,22,23]. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms" and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

Numerous other pathogens can cause monomicrobial (type II) necrotizing infection less frequently; Vibrio vulnificus and Aeromonas hydrophila deserve special comment. Infections due to these pathogens typically occur in the setting of traumatic injury associated with sea water or fresh water, respectively. Other risk factors for necrotizing infection due to V. vulnificus include cirrhosis and ingestion of contaminated oysters [24]. (See "Vibrio vulnificus infections".)

The incidence of necrotizing fasciitis ranges from 0.3 to 15 cases per 100,000 population [1,25]:

Polymicrobial (type I) necrotizing fasciitis (caused by aerobic and anaerobic bacteria) usually occurs in older adults and/or in individuals with underlying comorbidities. The most important predisposing factor is diabetes, especially with associated peripheral vascular disease. (See 'Risk factors' below.)

Monomicrobial (type II) necrotizing fasciitis (most commonly caused by GAS) may occur in any age group and in individuals with no underlying comorbidities [14]. In the United States, there are an estimated 3.5 cases of invasive GAS infections per 100,000 persons; necrotizing infections make up approximately 6 percent of these cases [26].

Necrotizing myositis — Necrotizing myositis is an infection of skeletal muscle typically caused by GAS (and other beta-hemolytic streptococci). It may be preceded by skin abrasions, blunt trauma, or heavy exercise [4,27-31]. Necrotizing myositis is rare. One report noted 21 cases documented between 1900 and 1985; another review of over 20,000 autopsies noted 4 cases [27,28].

Clostridial myonecrosis (gas gangrene) is discussed separately. (See "Clostridial myonecrosis".)

Necrotizing cellulitis — Necrotizing cellulitis is typically caused by anaerobic pathogens and may be divided into two types: clostridial (usually caused by Clostridium perfringens; less frequently Clostridium septicum) and nonclostridial (caused by polymicrobial infection).

In both types, crepitus is observed in the skin, but there is sparing of fascia and deep muscles. Pain, swelling, and systemic toxicity are not prominent features, and the relative mildness helps distinguish cellulitis from clostridial myonecrosis (gas gangrene). (See "Clostridial myonecrosis".)

RISK FACTORS — Necrotizing infection can occur among healthy individuals with no past medical history or clear portal of entry in any age group [14].

Risk factors for NSTI include [1,12,17,32-36]:

Major penetrating trauma

Minor laceration or blunt trauma (muscle strain, sprain, or contusion)

Skin breach (varicella lesion, insect bite, injection drug use)

Recent surgery (including colonic, urologic, and gynecologic procedures as well as neonatal circumcision)

Mucosal breach (hemorrhoids, rectal fissures, episiotomy)

Immunosuppression (diabetes, cirrhosis, neutropenia, HIV infection)

Malignancy

Obesity

Alcoholism

In women: pregnancy, childbirth, pregnancy loss, gynecologic procedures

Diabetes is a particularly important risk factor for necrotizing infection involving the lower extremities, perineum, and head and neck region [13,14]. In addition, use of sodium-glucose cotransporter 2 inhibitors (agents used for treatment of adults with type 2 diabetes) has been associated with NSTI of the perineum (Fournier gangrene) [37]. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Genitourinary tract'.)

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with development or progression of streptococcal necrotizing infection; data are conflicting [1,18,38-40]. Regardless of their role in pathogenesis, NSAIDs may mask signs and symptoms of inflammation in patients with NSTI, which may be associated with a delay in diagnosis.

CLINICAL MANIFESTATIONS

Typical findings — NSTI can include involvement of the epidermis, dermis, subcutaneous tissue, fascia, and muscle [1]. Necrotizing infection most commonly involves the extremities (lower extremity more commonly than upper extremity), particularly in patients with diabetes and/or peripheral vascular disease. Necrotizing infection usually presents acutely (over hours); rarely, it may present subacutely (over days). Rapid progression to extensive destruction can occur, leading to systemic toxicity, limb loss, and/or death [5,6,21]. Therefore, early recognition of necrotizing infection is critical.

Clinical manifestations of necrotizing infection include [1,2,6,41,42]:

Erythema (without sharp margins; 72 percent)

Edema that extends beyond the visible erythema (75 percent)

Severe pain (out of proportion to exam findings in some cases; 72 percent)

Fever (60 percent)

Crepitus (50 percent)

Skin bullae, necrosis, or ecchymosis (38 percent)

Fever (102 to 105°F), tachycardia, and systemic toxicity may be observed. Hypotension may be present initially or develop with progressive infection. Other symptoms include malaise, myalgias, diarrhea, and anorexia.

The subcutaneous tissue may be firm and indurated, such that the underlying muscle groups cannot be palpated distinctly [2]. Marked edema may produce a compartment syndrome with complicating myonecrosis requiring fasciotomy. Lymphangitis and lymphadenitis are infrequent. (See "Acute compartment syndrome of the extremities".)

The process progresses rapidly over several days, with changes in skin color from red-purple to patches of blue-gray. Within three to five days after onset, skin breakdown with bullae (containing thick pink or purple fluid) and frank cutaneous gangrene can be seen.

In the setting of surgical wound infection, NSTI is characterized by copious drainage, dusky and friable subcutaneous tissue, and pale, devitalized fascia.

In the setting of necrotizing fasciitis, diminished sensation to pain develops in the involved area, due to thrombosis of small blood vessels and destruction of superficial nerves in the subcutaneous tissue. This may precede the appearance of skin necrosis and provide a clue to the presence of necrotizing fasciitis [8]. Subcutaneous gas is often present in the polymicrobial (type I) form of necrotizing fasciitis, particularly in patients with diabetes [14].

Involved sites — Necrotizing fasciitis most commonly involves the extremities, as discussed in the preceding section. Other presentations include necrotizing fasciitis of the perineum (Fournier gangrene), head and neck region, and neonatal infection:

Perineum (Fournier gangrene) – Necrotizing fasciitis of the perineum, known as Fournier gangrene, can occur as a result of a breach in the integrity of the gastrointestinal or urethral mucosa [43,44]. Fournier gangrene is a form of polymicrobial (type I) infection. Fournier gangrene typically begins abruptly with severe pain and may spread rapidly to the anterior abdominal wall and the gluteal muscles. Men are more commonly affected than women. Involvement in men may include the scrotum and penis (picture 1); involvement in women may include involvement of the labia.

Head and neck region – Necrotizing fasciitis of the head and neck can result from a breach in oropharynx mucous membrane integrity following surgery or instrumentation or in the setting of odontogenic infection [45].

In one study including 45 patients with cervical necrotizing fasciitis, most were attributable to mixed aerobic and anaerobic bacteria. The majority of cases were of dental origin (78 percent); the remaining cases were of pharyngeal origin or occurred after surgery or trauma [46]. Fasciitis spread to the face (22 percent), lower neck (56 percent), and mediastinum (40 percent). In a separate study, 28 percent of patients with necrotizing fasciitis of the head and neck developed mediastinitis; factors that contributed to mediastinal involvement included prior corticosteroid use, infection by gas-producing microbes, and a pharyngeal focus of infection [47]. Cervical (head and neck) necrotizing fasciitis is usually a polymicrobial (type I) infection. However, monomicrobial (type II) infection due to group A Streptococcus (GAS) can also occur. (See 'Conditions, microbiology, and epidemiology' above.)

Other conditions that can occur in the setting of necrotizing infection involving the head and neck region include Ludwig's angina (submandibular space infection) and Lemierre syndrome (septic thrombophlebitis of the jugular vein). (See "Submandibular space infections (Ludwig's angina)" and "Lemierre syndrome: Septic thrombophlebitis of the internal jugular vein".)

Neonatal infection – Most cases of necrotizing fasciitis in neonates present with abdominal or perineal involvement and are often due to beta-hemolytic streptococci. Polymicrobial infection occurs less often. Associated conditions include omphalitis, balanitis (related to circumcision), and hernia repair [48-52].

Laboratory findings — Laboratory findings are generally nonspecific. Abnormalities may include leukocytosis with left shift, acidosis, coagulopathy, hyponatremia, elevated inflammatory markers (C-reactive protein and/or erythrocyte sedimentation rate), and elevations in serum creatinine, lactate, creatine kinase (CK), and aspartate aminotransferase (AST) concentrations [1,5,53-56]. Elevations in serum CK or AST concentrations suggest deep infection involving muscle or fascia (as opposed to cellulitis) [1].

NSTI cannot be predicted reliably using laboratory parameters, particularly in the setting of early infection. A tool called the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score has been described; it is based on laboratory indicators including white cell count, hemoglobin, sodium, glucose, creatinine, and C-reactive protein [57,58]. The tool has demonstrated variable sensitivity; it should not be used to rule out NSTI [57,59-61].

Blood cultures are positive in approximately 60 percent of patients with monomicrobial (type II) necrotizing fasciitis (eg, due to GAS or other beta-hemolytic streptococci) and are routinely positive in patients with necrotizing myositis [29]. The yield of blood cultures is lower among patients with polymicrobial (type I) necrotizing fasciitis; in one series, it was 20 percent [14]. In addition, blood culture results may not reflect all organisms involved [62]. (See 'Conditions, microbiology, and epidemiology' above.)

DIAGNOSIS

General approach — NSTI should be suspected in patients with soft tissue infection (erythema, edema, warmth) and signs of systemic illness (fever, hemodynamic instability) in association with crepitus, rapid progression of clinical manifestations, and/or severe pain (out of proportion to skin findings in some cases) (algorithm 1). Early recognition of necrotizing infection is critical; rapid progression to extensive destruction can occur, leading to systemic toxicity, limb loss, and/or death [5,6,21].

The diagnosis of necrotizing infection is established via surgical exploration of the soft tissues in the operating room, with physical examination of the skin, subcutaneous tissue, fascial planes, and muscle [1]. Surgical exploration is required to establish the presence of necrotizing infection, evaluate the scope of involvement, and to debride devitalized tissue. Surgical exploration should not be delayed when there is clinical suspicion for a necrotizing infection while awaiting results of radiographic imaging, culture results, or other diagnostic information. (See "Surgical management of necrotizing soft tissue infections".)

Intraoperative specimens should be sent for Gram stain and culture (in addition to histology) (table 1).

Radiographic imaging studies can be useful to help determine whether necrotizing infection is present but should not delay surgical intervention when there is crepitus on examination or rapid progression of clinical manifestations [5]. (See 'Radiographic imaging' below.)

Blood cultures (two sets) should be obtained prior to administration of antimicrobial therapy. Reasonable serum laboratory testing includes complete blood count with differential, chemistries, liver function tests, creatinine concentration, coagulation studies, creatine kinase concentration, lactate concentration, and inflammatory markers (C-reactive protein and/or erythrocyte sedimentation rate). (See 'Laboratory findings' above.)

Clinical factors that may make diagnosis of NSTI difficult include [1]:

Absence of fever – Fever may be absent; in some cases, this may be due to use of nonsteroidal anti-inflammatory drugs.

Absence of cutaneous manifestations – Patients presenting with no obvious portal of entry may present with infection that began deep in the soft tissues; superficial signs of infection may not appear until late in the course of disease.

Attribution of severe pain to alternative cause – Pain may be erroneously attributed to recent surgery or other known condition.

Nonspecific imaging tests – Radiographic imaging may demonstrate edema with no gas in the deep tissue; these findings may be attributed to noninfectious causes, thereby confounding the diagnosis.

Attributing systemic manifestations to other causes – Gastrointestinal symptoms (nausea, vomiting, diarrhea) may be early manifestations of toxemia due to group A streptococcal infection but may be wrongly attributed to other conditions.

Surgical exploration and debridement — Surgical exploration is the only way to establish the diagnosis of necrotizing infection. Findings on direct examination include swollen and dull-gray appearance of the fascia, thin exudate without clear purulence, and easy separation of tissue planes by blunt dissection (picture 2) [2].

Surgery should be performed at the center where the patient presented, provided an appropriately trained surgeon is available (rather than delaying care for transfer). Early debridement is associated with better outcomes; survival is significantly increased among patients taken to surgery within 24 hours after admission compared with those in whom surgery is delayed, and survival is further increased with earlier surgical intervention (eg, within six hours) [42,63,64].

Intraoperative specimens should be sent for Gram stain and culture (table 1).

Tissue biopsy may be obtained but is not required to establish the diagnosis of necrotizing infection. Characteristic pathologic features of necrotizing fasciitis include extensive tissue destruction, thrombosis of blood vessels, abundant bacteria spreading along fascial planes, and infiltration of acute inflammatory cells [65]. Characteristic pathologic features of necrotizing myositis include degeneration and necrosis of skeletal muscle fibers, infiltration of granulocytes, and numerous bacteria in areas of muscle necrosis (picture 3).

Issues related to surgical management of NSTIs are discussed further separately. (See "Surgical management of necrotizing soft tissue infections".)

Radiographic imaging — Radiographic imaging can be useful to help determine whether necrotizing infection is present but should not delay surgical intervention when there is crepitus on examination or rapid progression of clinical manifestations [5].

The best initial radiographic imaging exam is computed tomography (CT) scan (image 1 and image 2). The most useful finding is presence of gas in soft tissues, which is seen most frequently in the setting of clostridial infection or polymicrobial (type I) necrotizing fasciitis (table 1); this finding is highly specific for NSTI and should prompt immediate surgical intervention [12,66,67]. Other radiographic findings may include fluid collections, absence or heterogeneity of tissue enhancement with intravenous contrast, and inflammatory changes beneath the fascia.

Magnetic resonance imaging (MRI) is not as useful as CT for detection of gas in soft tissues. In addition, MRI can be overly sensitive; it tends to overestimate deep tissue involvement and therefore cannot be used to reliably distinguish between necrotizing cellulitis and deeper infection [68].

Ultrasound may be used for detection of localized abscesses and gas in tissues but has not been well studied in necrotizing fasciitis.

Frequently, imaging studies demonstrate soft tissue swelling; this finding is not specific since it is not possible to distinguish between swelling caused by infection, trauma, surgery, or inflammation. Therefore, in such cases, the diagnosis of necrotizing infection can be established only by surgical exploration.

DIFFERENTIAL DIAGNOSIS — Conditions included in the differential diagnosis include:

Cellulitis – Cellulitis presents with skin erythema, edema, and warmth. Fever may be present, but cellulitis is generally not associated with hemodynamic instability or exquisite tenderness. Elevations in serum CK or AST concentrations suggest deep infection involving muscle or fascia (as opposed to cellulitis). (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Pyoderma gangrenosum – Pyoderma gangrenosum may be difficult to distinguish from necrotizing fasciitis [62,69-72]. Distinguishing features are summarized in the table (table 2). The distinction is important because inappropriate surgical debridement of pyoderma gangrenosum can cause extension of the lesion, and inappropriate administration of immunosuppressive therapy may worsen necrotizing fasciitis. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)

Gas gangrene (clostridial myonecrosis) – Gas gangrene (clostridial myonecrosis) is an acute invasion of healthy tissue that occurs spontaneously or as a result of traumatic injury. Both gas gangrene and polymicrobial (type I) NSTI are associated with gas in the tissues. In gas gangrene, the Gram stain typically demonstrates gram-positive rods, while, in polymicrobial necrotizing fasciitis, the Gram stain typically demonstrates mixed aerobes and anaerobes (table 1). The distinction is important in that management of clostridial myonecrosis may require amputation, whereas management of necrotizing fasciitis requires debridement (but limb salvage may be possible). (See "Clostridial myonecrosis".)

Pyomyositis – Pyomyositis may be confused with necrotizing myositis. These conditions differ in that pyomyositis is characterized by abscess formation in skeletal muscle, while necrotizing myositis is characterized by gangrenous necrosis. These are distinguished by clinical and radiographic features. Pyomyositis is usually caused by S. aureus and is generally associated with less systemic toxicity than necrotizing myositis. (See "Pyomyositis".)

Deep venous thrombosis – Deep venous thrombosis (DVT) is characterized by extremity swelling, pain, and warmth; the pain is less extreme than in the setting of necrotizing infection. Fever may be present in DVT but is more common in the setting of soft tissue infection. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

TREATMENT

Clinical approach — Treatment of necrotizing infection consists of early and aggressive surgical exploration and debridement of necrotic tissue, together with broad-spectrum empiric antibiotic therapy and hemodynamic support. Administration of antibiotic therapy in the absence of debridement is associated with a mortality rate approaching 100 percent [12].

Surgical debridement — NSTI is a surgical emergency. Radiographic imaging studies should not delay surgical intervention when there is crepitus on examination or rapid progression of clinical manifestations.

The goal of operative management is to perform aggressive debridement of all necrotic tissue until healthy, viable (bleeding) tissue is reached. Inspection and debridement in the operating room should be continued every one to two days until necrotic tissue is no longer present [41]. For severe necrotizing infection involving the extremities, amputation may be needed to control the infection [12].

Issues related to surgical debridement and reconstruction procedures are discussed further separately. (See "Surgical management of necrotizing soft tissue infections".)

Antibiotic therapy — In general, empiric treatment of necrotizing infection should consist of broad-spectrum antimicrobial therapy, including activity against gram-positive, gram-negative, and anaerobic organisms [12]. Antibiotic therapy should be initiated promptly after obtaining blood cultures (algorithm 1).

Acceptable empiric antibiotic regimens include [2]:

A carbapenem:

Imipenem (adults: 1 g IV every 6 to 8 hours)

Meropenem (adults: 1 g IV every 8 hours; children and neonates with a postnatal age >7 days: 20 mg/kg per dose every eight hours),

Ertapenem (adults: 1 g IV every 24 hours)]

or

Piperacillin-tazobactam (adults: 3.375 g every 6 hours or 4.5 g every 8 hours; children and neonates with a postnatal age >7 days: 75 mg/kg per dose of the piperacillin component, not to exceed to a maximum of 3 g, every 6 hours)

PLUS

An agent with activity against methicillin-resistant S. aureus (MRSA; such as vancomycin or daptomycin) (table 3). In neonates and children, vancomycin (15 mg/kg/dose every six to eight hours) is the usual empiric antibiotic for MRSA; the six-hour dosing interval is employed for sicker children.

PLUS

Clindamycin, for its antitoxin and other effects against toxin-elaborating strains of streptococci and staphylococci (600 to 900 mg intravenously [IV] every eight hours in adults; 40 mg/kg per day divided every eight hours in children and neonates) [6,73-78] (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'General principles'.)

For patients who have particular exposures that may suggest infections with specific organisms, such as trauma in fresh water (Aeromonas) or sea water (V. vulnificus), it is appropriate to ensure that empiric therapy includes antimicrobial agents with activity against such organisms. (See "Aeromonas infections", section on 'Therapy' and "Vibrio vulnificus infections", section on 'Therapy' and "Soft tissue infections following water exposure".)

Due to concerns for multidrug resistance among some Enterobacteriaceae and lack of consistent availability, ampicillin-sulbactam and ticarcillin-clavulanate, respectively, are no longer recommended. Patients with hypersensitivity to carbapenems or piperacillin-tazobactam may be treated with either an aminoglycoside or a fluoroquinolone, plus metronidazole.

Antibiotic treatment should be tailored to Gram stain, culture, and sensitivity results when available [2]:

Group A streptococcal (GAS) or other beta-hemolytic streptococcal infection – Penicillin (4 million units IV every four hours in adults >60 kg with normal renal function or 300,000 units/kg per day divided every six hours in children) plus clindamycin (600 to 900 mg IV every eight hours in adults or 40 mg/kg per day divided every eight hours in neonates and children) [6].

Combination therapy with penicillin and clindamycin should be continued until patients are clinically and hemodynamically stable for at least 48 to 72 hours; thereafter, penicillin monotherapy may be administered.

Clostridial infection – Penicillin plus clindamycin (dosing as above). (See "Clostridial myonecrosis".)

Aeromonas hydrophila – (See "Aeromonas infections".)

Vibrio vulnificus – (See "Vibrio vulnificus infections".)

Polymicrobial infection – Vancomycin (table 3) plus a beta-lactam-beta-lactamase inhibitor.

Antibiotics should be continued until no further debridement is needed and the patient's hemodynamic status has normalized; this duration often consists of at least two weeks of treatment and must be tailored to individual patient circumstances [79].

Hemodynamic support — Hemodynamic instability may require aggressive supportive care with fluids and vasopressors. Intravenous fluid requirements may be high, and albumin replacement may be required in the setting of capillary leak syndrome associated with streptococcal toxic shock syndrome (TSS) [1]. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Evaluation and management of suspected sepsis and septic shock in adults".)

Intravenous immune globulin — We favor administration of intravenous immune globulin (IVIG) for patients with NSTI in the setting of streptococcal TSS. This approach is supported by a 2018 meta-analysis including five studies of patients with streptococcal TSS treated with clindamycin (one randomized and four nonrandomized), in which use of IVIG was associated with a significant reduction in 30-day mortality (33.7 to 15.7 percent) [80]. Similarly, in a subsequent prospective observational study of patients with NSTI due to GAS, use of IVIG was associated with reduced 90-day mortality [81]. Prior data from retrospective studies and statistically underpowered prospective trials have been inconclusive on the efficacy of IVIG for NSTI [82-84]. The combination of clindamycin and IVIG is likely efficacious by reducing circulating toxins produced by GAS [80].

Issues related to use of IVIG in the setting of streptococcal TSS are discussed separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin'.)

Perioperative care — Issues related to perioperative care and use of hyperbaric oxygen are discussed separately. (See "Surgical management of necrotizing soft tissue infections" and "Hyperbaric oxygen therapy", section on 'Infection'.)

PREVENTION — Close contacts of a patient with necrotizing infection due to group A Streptococcus (GAS) can become colonized with a virulent strain [85,86]. The likelihood of a secondary case of necrotizing fasciitis or toxic shock syndrome is very low but higher than for the general population [87,88].

Postexposure prophylaxis — The role of postexposure prophylaxis in reducing the likelihood of a secondary GAS infection is uncertain [89]. We suggest prophylaxis for highly susceptible individuals (such as immunocompromised individuals or patients with recent surgery) who are close contacts of a patient with necrotizing infection due to GAS. We use penicillin (250 mg orally 4 times daily) for 10 days in such patients. Alternative regimens have been suggested [90], however, the optimal antibiotic prophylaxis remains undefined.

Regardless of whether a close contact receives postexposure prophylaxis or not, it is imperative that they be educated about the signs and symptoms of invasive GAS infections and to seek immediate medical care if these clinical features develop within 30 days of diagnosis in the index case.

Evidence supporting use of postexposure prophylaxis is limited due in part to the relative rarity of necrotizing GAS infection, and it has not been studied in prospective, randomized trials. Nevertheless, we favor this approach because of the potential severity of the infection.

Issues related to prophylaxis for contacts are discussed further separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Prophylaxis for contacts'.)

Infection control — In addition to standard precautions, patients with invasive GAS infection associated with soft tissue involvement warrant droplet precautions and contact precautions [91]. Droplet and contact precautions may be discontinued after the first 24 hours of antimicrobial therapy.

OUTCOME — Necrotizing infection is associated with considerable mortality, even with optimal therapy [81]. Observational studies have reported the following mortality rates:

Polymicrobial (type I) necrotizing fasciitis – 21 percent [14]

Fournier gangrene – 22 to 40 percent [43,44,92]

Cervical necrotizing fasciitis – 22 percent [46]

Neonatal necrotizing fasciitis – 59 percent [48]

Monomicrobial (type II) necrotizing fasciitis – 14 to 34 percent [5,19,20]

Factors associated with increased mortality include [14,20,93,94]:

White blood cell count >30,000/microL; band neutrophils >10 percent

Serum creatinine >2.0 mg/dL (177 mmol/L)

Age >60 years

Streptococcal toxic shock syndrome

Clostridial infection

Delay in surgery for more than 24 hours

Infection involving the head, neck, thorax, or abdomen

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Gangrene (The Basics)")

SUMMARY AND RECOMMENDATIONS

Necrotizing soft tissue infections (NSTIs) include necrotizing forms of fasciitis, myositis, and cellulitis. These infections are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality. They may be categorized based on microbiology and presence or absence of gas in the tissues (table 1). Risk factors for NSTI include skin or mucosal breach, traumatic wounds, and diabetes or other immunosuppressing conditions. (See 'Introduction' above and 'Risk factors' above.)

Necrotizing fasciitis is an infection of the deep soft tissues that results in progressive destruction of the muscle fascia and overlying subcutaneous fat. Infection may be polymicrobial (type I) or monomicrobial (type II) (see 'Necrotizing fasciitis' above):

Polymicrobial (type I) necrotizing infection is caused by aerobic and anaerobic bacteria. It usually occurs in older adults and/or in individuals with underlying comorbidities including diabetes.

Monomicrobial (type II) necrotizing infection is most commonly caused by group A Streptococcus (GAS) (and other beta-hemolytic streptococci). It may occur in any age group and in individuals with no underlying comorbidities.

Necrotizing myositis is an infection of skeletal muscle typically caused by GAS (and other beta-hemolytic streptococci). Necrotizing cellulitis is typically caused by anaerobic pathogens and may be divided into two types: clostridial (usually caused by Clostridium perfringens) and nonclostridial (caused by polymicrobial infection). (See 'Necrotizing myositis' above and 'Necrotizing cellulitis' above.)

Clinical manifestations of NSTI include erythema, edema extending beyond the visible erythema, severe pain (out of proportion to exam findings in some cases), fever, crepitus, and skin bullae, necrosis, or ecchymosis. Systemic toxicity may be observed. Necrotizing infection most commonly involves the extremities (lower extremity more commonly than upper extremity) and usually presents acutely. Other presentations of necrotizing fasciitis include involvement of the perineum (Fournier gangrene), head and neck region, and neonatal infection. (See 'Clinical manifestations' above.)

NSTI should be suspected in patients with soft tissue infection (erythema, edema, warmth) and signs of systemic illness (fever, hemodynamic instability) in association with crepitus, rapid progression of clinical manifestations, and/or severe pain (out of proportion to skin findings in some cases) (algorithm 1). The diagnosis of necrotizing infection is established via surgical exploration of the soft tissues in the operating room, with physical examination of the skin, subcutaneous tissue, fascial planes, and muscle. (See 'Diagnosis' above.)

Radiographic imaging studies can be useful to help determine whether necrotizing infection is present but should not delay surgical intervention when there is crepitus on examination or rapid progression of clinical manifestations. The best initial radiographic imaging exam is computed tomography scan. Presence of gas in the tissues (seen most frequently in the setting of polymicrobial [type I] necrotizing fasciitis or clostridial infection) is highly specific for NSTI and should prompt immediate surgical intervention. (See 'Radiographic imaging' above.)

Treatment of necrotizing infection consists of early and aggressive surgical exploration and debridement of necrotic tissue, together with broad-spectrum empiric antibiotic therapy and hemodynamic support. (See 'Treatment' above.)

In general, empiric antibiotic treatment of necrotizing infection should consist of broad-spectrum antimicrobial therapy, including activity against gram-positive, gram-negative, and anaerobic organisms. Acceptable empiric antibiotic regimens include (see 'Antibiotic therapy' above):

A carbapenem or piperacillin-tazobactam plus

An agent with activity against methicillin-resistant Staphylococcus aureus plus

Clindamycin (for its antitoxin effects against toxin-elaborating strains of streptococci and staphylococci)

Antibiotic treatment should be tailored to Gram stain, culture, and sensitivity results when available.

Issues related to surgical management of NSTI and hemodynamic support are discussed separately (See "Surgical management of necrotizing soft tissue infections" and "Evaluation and management of suspected sepsis and septic shock in adults".)

For patients with NSTI in the setting of streptococcal toxic shock syndrome, we suggest administering intravenous immune globulin (Grade 2C). (See 'Intravenous immune globulin' above.)

Close contacts of a patient with necrotizing infection due to GAS can become colonized with a virulent strain. For highly susceptible individuals (such as immunocompromised individuals or patients with recent surgery) who are close contacts of a patient with necrotizing infection due to GAS, we suggest postexposure prophylaxis with oral penicillin (Grade 2C). (See 'Prevention' above.)

REFERENCES

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Topic 7662 Version 58.0

References

1 : Necrotizing Soft-Tissue Infections.

2 : Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America.

3 : Evaluation and Management of Necrotizing Soft Tissue Infections.

4 : Streptococcal myositis.

5 : Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A.

6 : Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment.

7 : Necrotizing fasciitis.

8 : Necrotizing fasciitis.

9 : Fatal necrotizing fasciitis caused by Haemophilus influenzae serotype f.

10 : Necrotizing myositis and septic shock caused by Haemophilus influenzae type f in a previously healthy man diagnosed with an IgG3 and a mannose-binding lectin deficiency.

11 : Necrotizing fasciitis caused by unencapsulated Haemophilus influenzae.

12 : Necrotizing soft-tissue infection: diagnosis and management.

13 : Clinical and microbiological features of necrotizing fasciitis.

14 : Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality.

15 : Fungal Infections Increase the Mortality Rate Three-Fold in Necrotizing Soft-Tissue Infections.

16 : Fournier's gangrene: a review of 1726 cases.

17 : Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles.

18 : Streptococcal infections of skin and soft tissues.

19 : Population-based surveillance for group A streptococcal necrotizing fasciitis: Clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Ontario Group A Streptococcal Study.

20 : Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden.

21 : Necrotising fasciitis due to group A streptococci in western Norway: incidence and clinical features.

22 : Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome.

23 : Group A streptococcal bacteremia: the role of tumor necrosis factor in shock and organ failure.

24 : Necrotising fasciitis caused by Vibrio vulnificus in the lower limb following exposure to seafood on the hand.

25 : Increasing incidence of necrotizing fasciitis in New Zealand: a nationwide study over the period 1990 to 2006.

26 : The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004.

27 : Streptococcal myositis.

28 : Peracute spontaneous streptococcal myositis. A report on 2 fatal cases with review of literature.

29 : Spontaneous gangrenous myositis induced by Streptococcus pyogenes: case report and review of the literature.

30 : Spontaneous streptococcal myositis associated with disseminated intravascular coagulopathy.

31 : Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. The Working Group on Severe Streptococcal Infections.

32 : Necrotising fasciitis.

33 : Epidemiology and outcome of necrotizing fasciitis in children: an active surveillance study of the Canadian Paediatric Surveillance Program.

34 : Bacterial complications of primary varicella in children.

35 : Invasive group A Streptococcus infections associated with liposuction surgery at outpatient facilities not subject to state or federal regulation.

36 : Risk Factors For Necrotizing Fasciitis And Its Outcome At A Tertiary Care Centre.

37 : Risk Factors For Necrotizing Fasciitis And Its Outcome At A Tertiary Care Centre.

38 : Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome?

39 : Fulminant myonecrosis due to Streptococcus pyogenes in a previously healthy patient.

40 : Assessing the relationship between the use of nonsteroidal antiinflammatory drugs and necrotizing fasciitis caused by group A streptococcus.

41 : Improved results from a standardized approach in treating patients with necrotizing fasciitis.

42 : Determinants of mortality for necrotizing soft-tissue infections.

43 : Fournier's gangrene.

44 : Fournier's gangrene: historic (1764-1978) versus contemporary (1979-1988) differences in etiology and clinical importance.

45 : Cervical necrotizing fasciitis: Systematic review and analysis of 1235 reported cases from the literature.

46 : Cervical necrotizing fasciitis: clinical manifestations and management.

47 : Factors associated with the mediastinal spread of cervical necrotizing fasciitis.

48 : Neonatal necrotizing fasciitis: a report of three cases and review of the literature.

49 : Necrotizing fasciitis.

50 : Neonatal necrotising fasciitis following superficial skin infection with community-associated methicillin-resistant Staphylococcus aureus.

51 : Diagnosis and Treatment of Pediatric Necrotizing Fasciitis: A Systematic Review of the Literature.

52 : Epidemiology and Outcomes of Hospitalized Children With Necrotizing Soft-Tissue Infections.

53 : Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis.

54 : Use of admission serum lactate and sodium levels to predict mortality in necrotizing soft-tissue infections.

55 : Necrotizing soft tissue infections--are they different in healthy vs immunocompromised children?

56 : A simple model to help distinguish necrotizing fasciitis from nonnecrotizing soft tissue infection.

57 : The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections.

58 : Utility of modified Laboratory Risk Indicator for Necrotizing Fasciitis (MLRINEC) score in distinguishing necrotizing from non-necrotizing soft tissue infections.

59 : A case of necrotizing fasciitis with a LRINEC score of zero: clinical suspicion should trump scoring systems.

60 : Application of the Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score to patients in a tropical tertiary referral centre.

61 : Necrotizing Soft Tissue Infection: Diagnostic Accuracy of Physical Examination, Imaging, and LRINEC Score: A Systematic Review and Meta-Analysis.

62 : Necrotizing fasciitis versus pyoderma gangrenosum: securing the correct diagnosis! A case report and literature review.

63 : Early diagnosis and treatment of necrotizing fasciitis can improve survival: an observational intensive care unit cohort study.

64 : Early surgical intervention and its impact on patients presenting with necrotizing soft tissue infections: A single academic center experience.

65 : Correlation of histopathologic findings with clinical outcome in necrotizing fasciitis.

66 : Diagnosis of necrotizing soft tissue infections by computed tomography.

67 : Necrotizing fasciitis of the head and neck: role of CT in diagnosis and management.

68 : Differentiation of necrotizing fasciitis and cellulitis using MR imaging.

69 : Postoperative Pyoderma Gangrenosum in Children: The Case Report of a 13-Year-Old Boy With Pyoderma Gangrenosum After Hip Reconstruction Surgery and a Review of the Literature.

70 : Postsurgical Pyoderma Gangrenosum Versus Necrotizing Fasciitis: Can We Spot the Difference?

71 : The diagnosis you wish you had never operated on: Pyoderma gangrenosum misdiagnosed as necrotizing fasciitis-a case report.

72 : Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

73 : The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis.

74 : Experimental approach to the problem of treatment failure with penicillin. I. Group A streptococcal infection in mice.

75 : Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inoculum effect.

76 : Invasive group A streptococcal infection: New concepts in antibiotic treatment.

77 : Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.

78 : Antibiotic effects on bacterial viability, toxin production, and host response.

79 : Less is more? Antibiotic duration and outcomes in Fournier's gangrene.

80 : Polyspecific Intravenous Immunoglobulin in Clindamycin-treated Patients With Streptococcal Toxic Shock Syndrome: A Systematic Review and Meta-analysis.

81 : Risk Factors and Predictors of Mortality in Streptococcal Necrotizing Soft-tissue Infections: A Multicenter Prospective Study.

82 : Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised, blinded, placebo-controlled trial.

83 : Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals.

84 : Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial.

85 : Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group.

86 : An outbreak of group A Streptococcal infection among health care workers.

87 : Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: recommendations from the Centers for Disease Control and Prevention.

88 : Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections.

89 : Nosocomial transmission of necrotising fasciitis.

90 : Invasive group A streptococcal disease: Management and chemoprophylaxis.

91 : 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings.

92 : Fournier's gangrene: experience with 25 patients and use of Fournier's gangrene severity index score.

93 : Predictors of mortality and limb loss in necrotizing soft tissue infections.

94 : Independent predictors of mortality for necrotizing fasciitis: a retrospective analysis in a single institution.