Chapter 179. Necrotizing Soft Tissue Infections: Necrotizing Fasciitis, Gangrenous Cellulitis, and Myonecrosis

Necrotizing skin and soft tissue infections (SSTI) include gangrenous cellulitis, necrotizing fasciitis, and anaerobic myonecrosis. All of these conditions are highly destructive locally, and they frequently have severe or lethal systemic complications; they must be recognized early and treated aggressively, usually with a combination of antibiotics, surgical debridement, and supportive measures. However, the infrequency of these infections, coupled with the relatively nonspecific clinical findings early in their course, makes rapid diagnosis difficult; up to 85% of these patients do not have an accurate diagnosis at the time of admission to the hospital.1

Necrotizing fasciitis, especially the monomicrobial form, frequently affects young, healthy patients. However, increased age, immunocompromise including acquired immunodeficiency syndrome (AIDS), chronic illness, alcoholism, and percutaneous drug use are risk factors.2 A chart review from New Zealand found that features common to a high proportion of necrotizing fasciitis patients included diabetes mellitus, gout, congestive heart failure, and recent surgical procedures. However, statistical analysis to assess the validity of these associations was not presented.3 Necrotizing fasciitis arising at sites of recent tattoos4,5 and sclerotherapy has been reported.6 Finally, the role of nonsteroidal anti-inflammatory drugs (NSAIDS) is controversial; many studies have found an association between NSAIDS and necrotizing SSTI, but prospective studies have failed to confirm the speculation that NSAIDS may promote infection progression or delay diagnosis by obscuring early symptoms.7

Clostridial necrotizing SSTI, including anaerobic cellulitis and myonecrosis, arise either from deep traumatic or surgical inoculation, or from hematogenous spread from an internal infectious focus.8 These infections are rare in healthy patients; common associations include malignancy, neutrophil dysfunction, bowel ischemia, and hemolytic-uremic syndrome.9

The most common pathogens mediating necrotizing SSTI are group A β-hemolytic Streptococcus (GAS) in the case of necrotizing fasciitis type II, and anaerobes such as clostridial species in the case of gangrenous cellulitis and myonecrosis. However, other relatively common organisms that cause necrotizing SSTI include Staphylococcus aureus, non-group A streptococcal species, Pseudomonas, Pasteurella, Vibrio, and Enterobacteriaceae (such as Escherichia coli).8,10 These infections are often polymicrobial, with a mix of both pathogens and contaminants (see Table 179-1).

The microorganisms associated with necrotizing cutaneous infections in the normal host are joined by a variety of other traditionally pathogenic and nonpathogenic bacteria, as well as fungi, in immunocompromised patients. In the presence of thermal burns, hematogenous Pseudomonas aeruginosa may infect normal skin, producing ecthyma gangrenosum (see Chapter 180), or may be attracted to burn areas, leading to extensive bacteremic pseudomonas gangrenous cellulitis. Mucormycotic gangrenous cellulitis can engraft onto thermal burns or complicate percutaneous catheter areas in immunosuppressed individuals. In the immunocompromised host, it becomes mandatory to biopsy any necrotic cellulitic lesions and to be alert to the possibility of a wide range of bacterial, viral, fungal, and even parasitic pathogens.

The pathophysiology of necrotizing fasciitis has not been fully elucidated, but the bacteria capable of producing this infection, including GAS, appear to share the ability to produce enzymes that degrade fascia and allow rapid proliferation at the level of the superficial fascia. This proliferation results in local thrombosis, progressive ischemia, liquefaction necrosis, and ultimately, more superficial gangrene.11

Mechanisms of clostridial virulence are better understood. Clostridial species are large spore-forming Gram-positive bacilli that produce more toxins than any other known bacteria.12 Clostridial α-toxin, a pore-forming lecithinase that mimics the function of phospholipase C, hydrolyzes cell membranes, and increases capillary permeability and platelet aggregation, thereby mediating hemolysis and dermonecrosis. This exotoxin has been shown to be both sufficient and necessary for gas gangrene in mouse models; injection of Bacillus subtilis carrying a gene for the toxin produces myonecrosis, and immunizing mice against the α-toxin prevents the infection.13 Nevertheless, other clostridial toxins do appear to play a role in human SSTI disease, including θ-toxin (containing perfringolysin O), ϵ-toxin, and multiple collagenases. Clostridium perfringens accounts for approximately 80% of clostridial SSTI; less common causes of gangrenous clostridial SSTI include Clostridium septicum, Clostridium novyi, and Clostridium sordellii.12,14

Necrotizing infections of soft tissues may be localized to the muscle, fascia, or the overlying skin and subcutis, or they may cross these layers; the structural layers involved provide a useful framework for categorizing these infections into gangrenous cellulitis (affecting the dermis and subcutaneous tissue), necrotizing fasciitis (predominantly affecting the fascia), and pyomyositis and myonecrosis (affecting the muscle) (Table 179-2).

History

Necrotizing fasciitis infections are often more extensive than the overlying skin changes would suggest. Early in the disease (stage 1), the involved area may be painful at first and then evolve with objective findings: swelling, erythema, warmth, and tenderness, resembling simple cellulitis.11 Constitutional symptoms with high fever and toxicity are characteristic of early progression, but at least one study of necrotizing fasciitis patients found fever in only half of patients, and hypotension in only 18%.15 It is possible that systemic manifestations are delayed or obscured by widespread use of broad-spectrum antibiotics at the first sign of a SSTI, when the disease is often thought to be a simple cellulitis.16 Within several days, induration worsens and bullae develop (stage 2). Ultimately, the skin color becomes purple and frank cutaneous gangrene ensues (stage 3) (Fig. 179-1). At this advanced stage, the involved area is no longer tender but has become anesthetic as a result of occlusion of small blood vessels and destruction of superficial nerves in the subcutaneous tissues.11,16–18

The classification of necrotizing fasciitis can be confusing because different variants have been described in the literature using unrelated criteria, including microbiologic features, anatomic location, and etiology.

Variants Defined by Microbiologic Characteristics

Type I Necrotizing Fasciitis

Type I necrotizing fasciitis, a polymicrobial infection, is caused by a mix of facultative and anaerobic microbes, often delivered into the subcutaneous tissues after surgery, trauma, bowel perforation from neoplasm or diverticulitis, or injecting drug abuse via skin popping. It is by far the most common form of necrotizing fasciitis, accounting for nearly 90% of cases, often occurring in patients compromised by diabetes or malnutrition. Organisms include at least one anaerobic organism recovered in a mix of facultative microbes: nongroupable Streptococci, Enterococci, anaerobic Streptococci and Staphylococci, Bacteroides, and Enterobacteriaceae including E. coli, as well as various aquatic bacteria. Often, three to five species contribute to the infection, which may have a slower pace than GAS in evolving to a full-blown process with cutaneous manifestations.19,20

Type I necrotizing fasciitis most commonly occurs on an extremity, abdominal wall, perineum, or near operative wounds (see Fig. 179-1). It is important to recognize that when this infection presents in the thigh (dissection along the psoas muscle) or abdominal wall, it may be secondary to an intestinal source (occult diverticulitis, rectosigmoid neoplasm). Crepitus often develops, particularly in patients with diabetes mellitus if gas-forming anaerobes, such as Bacteroides, are causative.

Type II Necrotizing Fasciitis and Streptococcal Gangrene

Type II necrotizing fasciitis is caused by a monomicrobial infection, usually GAS, which in this setting has been referred to as “flesh eating bacteria” by the lay press. If the process is not limited to the fascia, it is referred to as streptococcal gangrene. Occasionally, in the neonatal period, and very rarely in adults, group B Streptococci have been recovered.21 Other streptococcal species have been reported to cause monomicrobial necrotizing fasciitis, including groups C and G Streptococci, as well as Streptococcus pneumoniae.22 In addition, monomicrobial necrotizing fasciitis caused by methicillin-resistant S. aureus (MRSA) may be much more common than previously thought, with one recent study finding it to be the cause of nearly 40% of necrotizing fasciitis patients between 2001 and 2006.23

Patients may be immunocompromised by age or illness such as diabetes, alcoholism, or cirrhosis, but are usually healthy individuals. The location of the necrotizing lesion is most often an extremity and rarely, the face. The clinical presentation is usually indistinguishable from type I necrotizing fasciitis, but necrosis of the overlying skin can be particularly rapid and dramatic, revealing deeper structures, including tendon sheaths and muscle. Though lymphangitis is rare, metastatic abscesses can occur. Bacteremia is documented in approximately two-thirds of patients, and patients often develop a streptococcal toxic shock syndrome (see Chapter 177).24

Variants Defined by Extrafascial Structures Affected

Synergistic Necrotizing Cellulitis

Synergistic necrotizing cellulitis is a mixed infection of anaerobes and facultative bacteria generally classified as a type I necrotizing fasciitis because of prominent fascial involvement, but it actually may infect all soft-tissue structures, including skin and muscle. It is painful, progressive, and highly lethal, primarily affecting frail, elderly, diabetic, or obese patients, almost always with compromising cardiovascular and renal disease. The process may begin with only mild pain and low-grade fever, evolving slowly over 7–10 days. The initial skin lesion is a small reddish-brown bulla or patch on the perineum (near a perirectal or ischiorectal abscess) or lower extremity, with extreme local tenderness; the superficial appearance belies the widespread destruction of the deeper tissues. Skin sinuses (with surrounding areas of blue–gray gangrene) form, draining a foul-smelling thin pale “dishwater” exudate containing fragments of necrotic fat. Gas can be palpated in approximately one-fourth of patients. Half of the patients become bacteremic. Extensive gangrene of the superficial tissues and fat can be visualized by direct inspection through open skin areas or with skin incisions.25–27

Frequently isolated organisms include anaerobes (Streptococci and/or Bacteroides) and facultative bacteria, especially Enterobacteriaceae (E. coli, Proteus, and Klebsiella species).25,28 Rapid and extensive surgical debridement with antibiotics guided by the Gram stain is essential; nevertheless, the mortality rate remains in the 40%–50% range.27

Progressive Bacterial Synergistic Gangrene (Meleney Gangrene)

Progressive bacterial synergistic gangrene is a specific polymicrobial infection, perhaps best categorized as a form of synergistic necrotizing cellulitis, which presents with a necrotic ulcer at the site of abdominal or thoracic incisions, wire-stay sutures, or fistulous tracts. The infection typically develops insidiously, within a week or two of a procedure. It is called synergistic because by definition, two or more bacteria must coinfect to create the clinical appearance, as demonstrated by Meleney who reproduced these ulcers by injecting microaerophilic Streptococci and S. aureus into animal skin; the infection did not develop when either pathogen was injected alone.27

Variants Defined by Anatomic Location

Cervical and Craniofacial Necrotizing Fasciitis

These two variants of necrotizing fasciitis may be classified as either type I or type II, but they are defined and named by their anatomic location and etiology, rather than by their microbiologic profiles. Cervical necrotizing fasciitis is usually a type I infection (polymicrobial etiology), but GAS can be the single etiologic agent in rare cases, particularly in the setting of peritonsillar abscess formation. Most commonly, cervical necrotizing fasciitis originates from dental or pharyngeal sources. Crepitus may develop as the infection spreads to the face. This is in contradistinction to craniofacial necrotizing fasciitis, which starts in the face and is most commonly caused by GAS after a traumatic episode. Cervical necrotizing fasciitis carries a much higher mortality rate than the craniofacial variant.29–31

Fournier's Gangrene

Fournier's gangrene is a localized gangrenous SSTI involving the genitalia. The infection tends to be limited to skin and subcutaneous tissue of the genitals, but it may spread along fascial planes to the perineum and abdominal wall. It is usually caused by a mix of facultative and anaerobic organisms, and therefore is best categorized as a form of synergistic necrotizing cellulitis or type I necrotizing fasciitis. In rare cases, GAS as the single pathogen has been implicated, and this may be related to rectal ring carriage or to oral–genital sex. The average age at onset is 50–60 years of age. Most men have underlying diseases or a history of procedures. These include diabetes mellitus, ischiorectal abscess, perineal fistula, bowel disease (rectal or colon carcinoma, diverticulitis), scrotal or penile trauma, prior hemorrhoidal or urogenital surgery, pressure ulcers of the scrotum and perineum, paraphimosis and, rarely, obscure causes, such as dissection of pancreatic secretions through the retroperitoneum and into the scrotum in acute pancreatitis.32–34

The onset of Fournier's gangrene can be insidious, with a discrete area of edema, erythema, and necrosis on the scrotum. Ultimately, skin necrosis begins to proceed rapidly over 1–2 days (Fig. 179-2). Pain, swelling, and crepitus in the scrotum, perineum, or suprapubic region may be marked. Foul-smelling drainage occurs, indicating a contribution from anaerobes. Purple discoloration of the scrotum, an initial “red flag,” progresses to frank gangrene. The testes, glans penis, and spermatic cord are usually spared, as they have a separate blood supply. The infection may progress and invade the abdominal panniculus in obese patients, especially those with diabetes mellitus, leading to rapid and extensive destruction of tissue and requiring wide debridement and prolonged hospitalization. Fournier's gangrene carries 20% mortality even with treatment.32–34

Diagnostic Studies (Cultures, Histopathology, Imaging)

The gold standard for diagnosing necrotizing fasciitis is open surgical exploration with direct visualization and palpation of the necrotic fascia, which appears grayish and does not bleed; blunt dissection reveals foul-smelling discharge and a lack of usual adherence of the superficial fascia to underlying tissues.11 Short of open exploration, no test is specific for necrotizing infection, but several laboratory, microbiologic, histopathologic, and imaging studies have been shown to be useful in differentiating bacterial necrotizing SSTI from non-necrotizing infections or noninfectious causes of soft-tissue necrosis (see Box 179-1).

Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC)

In 2004, Wong et al performed a retrospective analysis to determine independent predictive factors of necrotizing fasciitis at time of presentation, and converted these factors into a scoring system they called Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC). The variables included in the score are elevated C-reactive protein, leukocytosis, anemia, hyponatremia, renal failure, and hyperglycemia; each is assigned a weight depending on the degree of abnormality. In this initial study, a score of at least six had a positive predictive value of 92%, and a score of at least eight was strongly predictive of necrotizing fasciitis. The negative predictive value for a score less than six was 96%.35 This system may be useful for stage 1 disease, when the clinical presentation is generally identical to cellulitis, but a recent analysis of the LRINEC in a tropical tertiary care center found significantly lower sensitivity (80%) and specificity (67%) at a cutoff value of six.36

Another diagnostic test that has shown some promise is tissue oxygen monitoring by near-infrared spectroscopy. A cutoff oxygen saturation of less than 70% was found to be highly sensitive (100%) and specific (97%) for necrotizing fasciitis in patients without known chronic venous stasis, peripheral vascular disease, shock, or systemic hypoxia.37

Biopsy for Culture and Histopathology

Tissue from a biopsy or surgical specimen is far more likely to demonstrate an organism on stain or culture in necrotizing SSTI than in simple cellulitis. One study of 198 necrotizing SSTI was able to obtain microbiologic data in 189 of the samples.38

Deep incisional biopsy and histopathologic examination on frozen section has been shown to decrease mortality in necrotizing fasciitis by rapidly establishing the diagnosis and thus defining the need for surgical debridement.39 Indications for an open exploration and a biopsy include confusion, pain and tenderness, tachycardia, tachypnea, ketoacidosis/hyperglycemia, bullous or gangrenous skin changes, bronzing of the skin, spreading areas of anesthesia, thin reddish discharge with undermining of wound edges, crepitus, and an abscess with multiple tracts.

In streptococcal gangrene, the prominent angiitis and focal dermal necrosis with spread along fascial planes suggest that the disease is fundamentally gangrene of the subcutaneous tissues followed by necrosis of the overlying skin. Microscopically, fibrinoid necrosis is present in the media of many arteries and veins passing through the edematous and damaged fascia.40 Fibrin thrombi and coagulation necrosis may be present throughout the fascia and skin. Numerous polymorphonuclear leukocytes and mononuclear cells infiltrate the lesion, and the upper layers of the dermis contain large numbers of Gram-positive cocci.

Imaging

Several imaging modalities, including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound have all been shown to demonstrate distinctive imaging features of necrotizing fasciitis lesions, but their role in diagnosis is still controversial. All three of these modalities can show fascial thickening, as well as fluid and gas in the adjacent tissue planes.11 MRI is the most sensitive of these studies, and may also show a hyperintense T2-weighted signal in the muscle, and a deep dermal, dome-shaped area of increased signal.11,41 However, the sensitivity of MRI is higher than the specificity, resulting in an excellent negative predictive value, but a relatively high false-positive rate, resulting in some unnecessary surgical explorations.42 While these studies, especially MRI, can be helpful in ruling-out necrotizing fasciitis, or in differentiating early disease from simple cellulitis, radiographic testing should never delay open surgical examinations in cases with a high index of suspicion.

Prognosis and Clinical Course

Although subacute variants have been described, necrotizing fasciitis generally follows a hyperacute progression that results in rapid shock and multiorgan failure.1 The mortality rate ranges in the literature from 17%–49%.43,44 The wide range of mortality for necrotizing fasciitis and all necrotizing SSTI depends largely on the underlying health and immune status of the patients, and on the extent of diagnostic delay.

Histopathologic features can predict prognosis, with mortality increasing as the bacteria in the tissue increase and the number of neutrophils decrease.16 Delay in diagnosis and comorbid streptococcal toxic shock syndrome are associated with particularly poor survival.43 Other factors associated with decreased survival in individual studies include age greater than 50, tachycardia, fever, leukocytosis, renal failure, hematocrit greater than 50%,45 APACHE II score of at least 13,44 congestive heart failure, and a history of gout.3

Nonclostridial Crepitant Cellulitis

The patient with nonclostridial crepitant cellulitis may have experienced a traumatic or surgical injury that was inadequately debrided or had an underlying local infection, a poorly performed needle stick, or skin popping (injecting drug use into dermal or subcutaneous tissue).46,47 Underlying diabetes, glucocorticoid or NSAID use, and granulopenia may be present. The clinical presentation is often insidious, with low-grade fever, mild pain, and tenderness, but with early palpable gas and edema. Anaerobic nonspore-forming isolates may include Bacteroides sp. or Peptostreptococci, often with facultative Gram-negative bacilli. In uncontrolled diabetes mellitus, the presence of gas may result from metabolism of glucose by E. coli, Klebsiella, Aeromonas, and other microorganisms10 (see Chapter 180).

Clostridial Anaerobic Cellulitis

The histotoxic clostridia are responsible for a variety of infections that involve the subcutaneous and muscular tissues, often with abrupt and dramatic changes in the overlying skin.

Clostridial anaerobic cellulitis begins as an infection of the more superficial subcutaneous zone, but it may progress to involve deeper structures including deep fascia and muscle. The human gut commensal, C. perfringens, with or without other bacteria, is the most common cause. The cellulitis usually arises in tissues that are already devitalized, such as dirty or inadequately debrided wound several days after injury, needle stick, or surgery. The clostridia are able to grow in the wound and extend rapidly through tissue planes with attendant formation of large quantities of gas that is both readily palpable and visible on conventional X-ray. A thin, dark-gray to brown, foul, serous discharge is often produced.48 Gram stain of the drainage reveals short, plump, blunt-ended, “box-car” shaped Gram-positive rods with a variable number of polymorphonuclear leukocytes and, occasionally, other bacterial forms.8

Compared with anaerobic myonecrosis, anaerobic cellulitis is more indolent, produces less surface change and relatively little local pain, edema, or toxemia. At surgery, gas may be readily evident throughout the exudate. Anaerobic cellulitis can be distinguished from anaerobic myonecrosis by inspection of muscle to avoid needless mutilating surgery and amputations.

Other variants of anaerobic cellulitis are more commonly associated with toxemia. C. novyi and C. sordellii are specifically associated with infected wounds from intravenous drug use, childbirth, and medical abortions. Patients develop toxic shock and gangrenous cellulitis, though fever is not universally seen. The organism can usually be cultured from wounds, but blood cultures may remain negative.49,50 The environmentally resident C. septicum can cause a toxic anaerobic cellulitis arising via hematogenous spread from a gastrointestinal source.

Infectious myositis is a broad term for skeletal muscle infection with any pathogen, including viruses, bacteria, fungi, and parasites. Bacteria and fungi tend to cause a local myositis, which is referred to as pyomyositis in the presence of a purulent collection. Cases of pyogenic myositis are generally divided into clostridial and nonclostridial etiologies.51 The most common nonclostridial causes of pyomyositis and myonecrosis are S. aureus and β-hemolytic streptococcal species. GAS may cause myositis with severe muscle edema, necrosis, compartment syndrome, and overlying skin changes from deep ischemia.52,53 Other potential pathogens include S. pneumoniae, Haemophilus influenza, Gram-negative bacilli, Mycobacteria, and fungi.10,43,54 Bacteremia is documented in 5%–30% of pyomyositis cases.43

Clostridial myositis can produce a crepitant myonecrosis, often referred to as “gas gangrene.” Uncommonly, nonclostridial pathogens such as Aeromonas hydrophila, Peptostreptococcus, and Bacteroides species can cause a similar crepitant myonecrosis.54

Classical Anaerobic (Clostridial) Myonecrosis (Gas Gangrene)

Anaerobic myonecrosis (gas gangrene) is a rapidly progressing, toxemic, potentially lethal infection involving muscle but with secondary changes in the overlying skin. Gas gangrene may also occur in the uterus, intraperitoneal viscera, brain, and eye, sometimes in the absence of bacteremia. The infection may develop as a complication of a traumatic dirty wound with extensive muscle and soft-tissue damage,31 or after surgery on the bowel or gallbladder. C. perfringens is the most common pathogen in the classic presentation of anaerobic myonecrosis.

The incubation period of anaerobic myonecrosis is often short (12–24 hours) but may be delayed, rarely developing after anaerobic cellulitis. The first symptom is usually severe local pain followed by fever, tachycardia, and hypotension. Gas formation is present but not prominent in subcutaneous tissues, and may be obscured by edema of the superficial tissues. Radiography reveals extensive dissection of gas through the deep soft tissue structures.55

The skin often takes on a dark yellow or bronze discoloration with tense blebs or bullae containing dark brown fluid. A serosanguineous exudate can be expressed from the wound or aspirated from a bulla. Gram stain of the exudate reveals plump Gram-positive rods and rare or absent white blood cells, even with a systemic leukocytosis. This paucity of leukocytes is notable on muscle biopsy as well, perhaps a result of the θ-toxin (perfringolysin O), which appears to inhibit recruitment of neutrophils.56 The overlying skin may develop patchy necrosis and desquamation, as a result of vascular compromise and local ischemia. At surgery, the process in the muscle is evident, with gray pallor, absence of bleeding, presence of gas, and failure of the muscle to respond to direct stimuli.8,43,54

Published mortality rates are generally in the 20%–30% range, but this rate increases dramatically in older patients, or in those with comorbid conditions or delayed diagnosis.57,58

Spontaneous, Nontraumatic Anaerobic Myonecrosis

In the absence of an external wound, septicemic gas gangrene may occur spontaneously, usually caused by C. septicum and often associated with hematologic malignancies or occult colon cancer, especially in the cecal area. Spontaneous C. septicum gas gangrene is a fulminant disease, with a mortality approaching 100% and marked by a precipitous onset and progression, often with subcutaneous gas, myonecrosis, and high-grade septicemia. Overlying skin of an involved area becomes red–brown and the epidermis sloughs early in the illness. In addition, the organism may be aerotolerant and thus lacks susceptibility to hyperbaric oxygen. No controlled treatment trials exist for this disease.59–61

Spontaneous gas gangrene from E. coli has also been reported. All three patients had cirrhosis, and no obvious source of bacteremia was noted.10 In addition, sterile, spontaneous diabetic myonecrosis is important to consider in the differential diagnosis, although these patients are usually not febrile and do not appear toxic. This entity is most common in women with late-stage diabetes mellitus, complicated by nephropathy and retinopathy, and it usually affects the quadriceps and thigh muscles, occasionally with slight elevation in muscle enzymes.62

Treatment of all necrotizing SSTI involves a combination of urgent debridement, antibiotics, and often, adjunctive therapies.

Antimicrobial treatment decisions for patients with crepitant or gangrenous SSTI must be based on a rapid or presumptive identification of the etiologic agent(s) (see Box 179-2). Until definitive microbiologic data is obtained, high-dose parenteral broad-spectrum antibiotics should be given to cover any pathogens on the clinical differential. An organism found on blood culture does not rule out the possibility of a polymicrobial infection, and should not necessarily prompt narrowing of the antimicrobial coverage until reliable cultures from the wound are obtained.

As a general rule, streptococcal infections should be treated with a regimen that includes penicillin G. Clindamycin should be added if toxic shock syndrome is suspected (see Chapter 177). Staphylococcal species should be treated with a penicillinase-resistant β-lactam, such as nafcillin, or with vancomycin, if MRSA is suspected. Alternative agents for empiric coverage of suspected MRSA include linezolid, daptomycin, tigecycline, and quinupristin-dalfopristin, as well as several agents still under development (see Chapter 178). Once cultures with susceptibility data are obtained, fluoroquinolones, sulfonamides, and other antibiotic classes may have a role. Clostridial infections should be treated with a combination of parenteral penicillin G and either clindamycin or metronidazole. Clindamycin-resistant C. perfringens SSTI has been reported.

Treatment of all types of necrotizing SSTI requires early and complete surgical debridement of necrotic tissue, including any skin, fascia, or muscle involved. In some cases, amputation of a limb can be rapidly accomplished and may be lifesaving in selected patients. Intraoperative inspection can help determine the depth of the infection, and should also provide material for bacterial and pathologic study. Re-exploration and debridement should be performed as necessary to ensure that all necrotic tissue has been removed.

Preoperative hyperbaric oxygen (HBO) has emerged as an important adjunctive therapy for several necrotizing SSTI, especially anaerobic infections such as clostridial cellulitis and myonecrosis.63 It has been postulated that HBO acts synergistically with many antibiotics, and that it restores the free radical-mediated antibacterial mechanisms of leukocytes in hypoxic tissue.64 It also appears to cease clostridial production of α-toxin and to directly suppress clostridial growth, and has been demonstrated by retrospective analysis to decrease mortality.65

Other adjunctive considerations in treatment of SSTI include the use of intravenous γ globulin for type II necrotizing fasciitis caused by GAS, but evidence for its benefit in the absence of toxic shock syndrome is lacking. There may be a role for granulocyte-stimulating stem cell factor,9 calcium–channel blockers, glycoprotein IIb/IIIa inhibitors,66 and photodynamic therapy,67 but data for all of these adjunctive therapies is limited.

As discussed above, there is some evidence that NSAIDs should be avoided in patients suspected of incubating or expressing early bacterial infections, but this remains controversial since prospective studies have failed to confirm the link between NSAIDs and severe SSTI thus far. C. perfringens antitoxins are no longer available for use in humans.