Necrotizing Soft-Tissue Infections

NSTIs represent a spectrum of infectious processes that are extensive and rapidly progressive. Based on the depth of skin and soft-tissue involvement, NSTIs are divided into three categories: necrotizing cellulitis, necrotizing fasciitis, and myonecrosis. Table 135-1 shows the classification of NSTIs. The sine qua non of these infections is necrosis of subcutaneous tissue, fascia, and muscle, with widespread undermining of the skin. The lack of anatomic boundaries and the fact that the infection is deep to the skin helps account for the severity of the infection as well as the frequent delay in its recognition. The trunk, extremities, and perineum are the most common sites of NSTIs, but other anatomic sites may be involved. For example, intraabdominal abscess, bowel perforation, and pancreatitis can present as necrotizing infection of the abdominal wall or extend into the thigh along the psoas muscle.^1,² Similarly, cervical fasciitis due to dental or neck abscess can extend to the mediastinum.

TABLE 135-1 Classification of Necrotizing Skin, Soft-Tissue, and Muscle Infections

Disease	Bacteriology	Comments
Necrotizing Cellulitis
Clostridial cellulitis	Clostridium perfringens	Local trauma, recent surgery; fascial/deep muscle spared
Nonclostridial cellulitis	Mixed: Escherichia coli, Enterobacter, Peptostreptococcus spp., Bacteroides fragilis	Diabetes mellitus predisposes; produces foul odor
Meleney’s synergistic gangrene	Staphylococcus aureus, microaerophilic streptococci	Rare infection; postoperative; slowly expanding, indolent, ulceration in superficial fascia
Synergistic necrotizing cellulitis	Mixed aerobic and anaerobic, including B. fragilis, Peptostreptococcus spp.	Diabetes mellitus predisposes; variant of necrotizing fasciitis type I; involves skin, muscle, fat, and fascia
Necrotizing Fasciitis
Type I	Mixed aerobic and anaerobic; staphylococci, B. fragilis, E. coli, group A streptococci, Peptostreptococcus spp., Prevotella, Porphyromonas spp., Clostridium spp.	Usually requires a breach in the mucous membrane layer either through surgery or penetrating injuries or from chronic medical conditions such as diabetes, peripheral vascular disease, malignancy, and anal fissures
Type II	Group A streptococci	Increasing in frequency and severity since 1985; very high mortality; often begins at site of nonpenetrating minor trauma such as a bruise or muscle strain but often no identified precursor
		Predisposing factors: blunt/penetrating trauma, varicella (chickenpox), intravenous drug abuse, surgical procedures, childbirth, NSAID use
Myonecrosis
Clostridial myonecrosis	Clostridium spp.	Predisposing factors: deep/penetrating injury, bowel and biliary tract surgery, improperly performed abortion and retained placenta, prolonged rupture of the membranes, and intrauterine fetal demise or missed abortion in postpartum patients. Recurrent gas gangrene occurs at sites of previous gas gangrene.
Streptococcal myonecrosis	Streptococci
Special Type of Necrotizing Soft-Tissue Infection
Fournier’s gangrene	Polymicrobial, with E. coli the predominant aerobe and Bacteroides the predominant anaerobe. Other microflora: Proteus, Staphylococcus, Enterococcus, aerobic and anaerobic Streptococcus, Pseudomonas, Klebsiella, and Clostridium	Necrosis of the scrotum or perineum that starts with scrotal pain and erythema and rapidly spreads onto anterior abdominal wall and gluteal muscle. It is more often seen in diabetics and can be associated with trauma.

Many different descriptive terms and eponyms have been used to describe NSTIs. The most common infections encountered in ICU patients are postoperative progressive bacterial synergistic gangrene, clostridial cellulitis, synergistic gangrene, necrotizing fasciitis, Fournier’s gangrene, gas gangrene, and Meleney’s synergistic gangrene. Although the terminology and depth of infection may be different, the severity and emergent need for surgical intervention are common to all varieties of these infections.

Pathogenesis

Pathophysiologic factors involved in the development and progression of NSTIs are host resistance, bacterial pathogens involved, and local barrier factors.

Bacterial Pathogens

There are specific bacteria that are more likely than others to cause NSTIs, as shown in Table 135-1. Although necrotizing cellulitis and fasciitis may be caused by a single bacterial pathogen such as group A Streptococcus, Vibrio spp., or zygomycetes, about 80% of necrotizing cellulitis or fasciitis results from polymicrobial infections with synergistic facultative aerobes and anaerobic gas-forming organisms. An average of 4.4 organisms are isolated from polymicrobial necrotizing infections.³ The former includes gram-positive and gram-negative aerobes such as Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, or Pseudomonas aeruginosa, and the latter includes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus.⁴ Certain predisposing conditions can be correlated with specific bacteria—for example, trauma with Clostridium spp., diabetes mellitus with Bacteroides spp., S. aureus, and Enterobacteriaceae, and immunosuppression with Pseudomonas spp. and Enterobacteriaceae.⁵

Traditionally, gas gangrene is synonymous with clostridial infection, and gas in the soft tissue is thought to be a grave finding. The majority of gas-producing infections do not involve Clostridium spp. but are instead necrotizing infections due to other bacterial pathogens. Many bacteria, especially facultative gram-negative bacilli (e.g., E. coli), produce insoluble gases such as hydrogen, nitrogen, and methane whenever they are forced to use anaerobic metabolism. Thus, the presence of crepitus in a soft-tissue infection on physical examination or radiographs implies anaerobic metabolism and existence of an NSTI.

Local Barrier Failure

Most serious soft-tissue infections require some degree of tissue injury and break in the skin to establish infection. The break in the skin may be due to a surgical incision or trauma; it may be related to large wounds or very small ones. The tissue injury may be due to either blunt or penetrating trauma of any kind. However, in a significant percentage of cases, it is difficult to find evidence of a break in the skin or soft-tissue trauma.

Clinical Manifestations and Diagnosis

The critical aspect of diagnosing NSTIs is maintaining a high index of suspicion, which allows for early recognition of the nonlocalized necrotizing nature of the infection and the need for surgical intervention. Although necrotizing cellulitis and fasciitis may occur after significant tissue trauma or a relatively trivial injury, up to 40% of NSTIs have no identifiable cause. NSTIs with identifiable barrier failure are more likely to be polymicrobial and are easier to diagnose than the more virulent infections caused by a single organism. In necrotizing cellulitis, gas is invariably found in the skin, but the fascia and deep muscle are spared. Early clinical findings are similar to those of common wound infections, including local edema (89%), erythema (30%), fever (71%), and local cutaneous anesthesia (27%) due to cutaneous nerve necrosis.⁶ These are followed by gangrenous skin changes with rapid extension beyond the borders of the original infection. Synergistic polymicrobial necrotizing fasciitis is characterized by “dishwater pus.” Patients usually have high fever, but no obvious source of clinical infection can be detected. Pain in the area of infection is usually out of proportion to the physical findings. As the infection progresses, patients develop shock and multiple organ failure. Mortality rates are high, with necrotizing fasciitis being fatal in 23.5% of cases.⁷

Clostridial myonecrosis typically develops within 12 to 24 hours after a traumatic event or closure of a deep contaminated wound. Recurrent gas gangrene caused by C. perfringens has been described in individuals with nonpenetrating injuries at sites of previous clostridial myonecrosis, where spores of C. perfringens remain quiescent in tissue and then germinate when minor trauma provides conditions suitable for growth. Patients present with the triad of severe pain, tachycardia out of proportion to fever, and crepitus in the soft tissue. Once overt gangrene with edema and bronze, purplish, or brown discoloration with bullae and watery discharge occur, the disease is at an advanced stage. Gram stain of the exudate shows gram-positive rods occasionally accompanied by other flora. In contrast, streptococcal myonecrosis usually develops over 2 to 4 days after trauma or closure of a wound. The onset is not as rapid, patients do not appear as sick, pain is not as severe, and gas formation is not as obvious as in those with clostridial myonecrosis.

Management

Initial management of NSTIs involves aggressive fluid resuscitation, appropriate broad-spectrum parenteral antibiotics, and most importantly, expedient and radical surgical débridement. Other adjunctive therapies such as hyperbaric oxygen and immunoglobulin have been used, but their efficacy has not been as well established.

Antibiotics

For type I necrotizing fasciitis (mixed aerobic and anaerobic), antibiotic treatment should be guided initially on results of the Gram stain. Early empirical treatment should be initiated with extended-spectrum penicillins (e.g., ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanic acid) or carbapenem antibiotics (e.g., imipenem-cilastatin). If there is a suspicion that resistant coliforms might be participating, such as in patients who have been hospitalized or who have been treated with antibiotics recently or where there is suspicion of rectal or intestinal involvement, a third-generation cephalosporin, aminoglycoside, or aztreonam combined with either clindamycin or metronidazole may be used. For those patients with severe cases or in whom clostridia are suspected, clindamycin in addition to penicillin is useful for inhibiting toxin production. The incidence of both community- and hospital-acquired methicillin-resistant S. aureus (MRSA) is increasing, and consideration of anti-MRSA treatment should be based on patient history and local resistance patterns. Nosocomial infections should be empirically treated.

Although there are no data from clinical trials establishing the benefit of combined therapy in type II necrotizing fasciitis (group A streptococci), penicillin G combined with clindamycin is the antibiotic therapy of choice. Clindamycin, but not metronidazole, is recommended not for its antianaerobic properties but because of its additional activity against gram-positive organisms, including specific inhibition of toxin production.⁸ Cefotaxime and ceftriaxone are acceptable alternatives. For patients allergic to penicillin, vancomycin is the recommended treatment.

Surgical Intervention

Early surgical débridement is critical in the management of NSTIs. Aggressive surgical excision of all involved tissue with a margin of normal-appearing tissue is mandatory. All necrotic tissue should be excised back to healthy bleeding margins. Additional incisions parallel to cutaneous nerves and blood vessels may be used to assess fascial viability without elevating the skin. The wound should be frequently reexamined for viability of tissue and repeat operative débridement is frequently required. Aggressive fascial débridement of abdominal surgical wounds may necessitate the use of prosthetic material to replace an abdominal wall defect, as depicted in Figure 135-1. In Fournier’s gangrene and perineal/perirectal NSTI, a colostomy for fecal diversion may be necessary to keep the wound clean. The testes generally survive because their blood supply is usually spared, but they may need to be temporarily implanted in the soft tissue of the medial thighs if the scrotum must be débrided. On rare occasion, NSTI of the extremities may require amputation.

Figure 135-1 Necrotizing fasciitis of the abdominal wall after extensive débridement and application of porcine dermal collagen implant for temporary abdominal closure (left) and after healing of anterolateral thigh flaps to reconstruct the abdominal wall (right).

Myonecrosis or gas gangrene requires radical débridement to viable muscle. When this process involves the extremities, control of the infection is more easily achieved, although as mentioned previously, amputation may be necessary. In contrast, clostridial myonecrosis involving the trunk may present some very difficult therapeutic decisions because the removal of nonviable tissue may leave the peritoneal or thoracic cavities open and their contents exposed. Temporary coverage with prosthetic materials may be necessary. Trunk infections are therefore associated with a grim prognosis.

Adjunctive Therapy

Hyperbaric Oxygen

The use of hyperbaric oxygen (HBO) in NSTIs is controversial. Although there are no randomized prospective studies of HBO in these infections, in vitro data and reviews of clinical series seem to show beneficial effects of HBO when combined with antibiotics and surgical débridement in the management of clostridial infection.^9,¹⁰ Hyperbaric oxygen is toxic to clostridia and inhibits bacterial growth, blocks production of alpha toxin, and preserves marginally perfused tissue. Debate also exists about the use of HBO for nonclostridial necrotizing skin and soft-tissue infection. In one report, the addition of HBO to the surgical and antimicrobial treatment of nonclostridial necrotizing fasciitis significantly reduced mortality and the need for débridement.⁹

Intravenous Immunoglobulin

Intravenous immunoglobulin (IVIG) has been administered to patients with streptococcal and staphylococcal toxic shock syndrome and may be efficacious in the treatment of this toxin-mediated disorder. Some studies have demonstrated IVIG has some beneficial effect in the treatment of NSTIs, theoretically owing to its neutralization of circulating clostridial toxins and streptococcal superantigens.¹¹ However, a large multicenter retrospective cohort study of children with streptococcal toxic shock syndrome showed no improvement in outcomes with administration of IVIG.¹² There is no clear consensus at this time regarding the efficacy of IVIG.

Important Soft-Tissue Infections of the Head and Neck

Ludwig’s Angina

In 1836, German physician Wilhelm Frederick von Ludwig described five patients with gangrenous induration of the connective tissues of the neck that progressed rapidly to involve the tissues covering the muscles between the larynx and the floor of the mouth.¹³ Ludwig’s angina is a potentially life-threatening, rapidly progressive, diffuse “woody” or brawny cellulitis of the submandibular and sublingual spaces that occurs most often in young adults with dental infections.

Pathogenesis

In adults, 50% to 80% of cases of Ludwig’s angina are caused by dental caries, and the disease has a mortality rate of 5% to 10%.¹⁴ Submandibular and sublingual spaces freely communicate, and with involvement of the deep cervical fascia, infection may spread rapidly, with grave consequences. Extension along the carotid sheath or the retropharyngeal space can cause mediastinitis.¹⁵ Infection is commonly caused by oral cavity anaerobes such as Fusobacterium, anaerobic streptococci, Bacteroides, spirochetes, and hemolytic Streptococcus organisms, although the infection may be mixed with Staphylococcus and Streptococcus, Klebsiella, or a combination of aerobic or anaerobic organisms.¹⁶ The presence of anaerobes commonly accounts for the occurrence of gas in the tissues.