NECROTIZING FASCIITIS

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INFECTIOUS DISEASES IN DERMATOLOGY

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NECROTIZING FASCIITIS The Changing Spectrum David R. Stone, MD, and Sherwood L. Gorbach, MD

Necrotizing fasciitis, first described by Wilson in 1952,@is one of the most dramatic infections a physician will ever come in contact with. Fortunately, this condition is quite rare, with approximately 500 to 1500 cases in the United States per year, of which 50 to 150 cases are due to group A Streptococc~s.~ With the emergence of highly invasive, toxicshock-producing strains of group A Streptococcus, a bad disease has taken a turn for the worse.7*1 3 r 1 * It is imperative that physicians be familiar with the presentation, aggressive in the medical or surgical approach to diagnosis and treatment, and knowledgeable about current antibiotic recommendations. Delay in the diagnosis and treatment of this disease is associated with high mortality in the range of 30% to 700/o. 9,37 Skin and soft tissue infections can be classified by the maximal depth of involvement, the presence or absence of necrosis, and the organisms present. Consideration must be given to whether multisystem organ failure or a toxic-shock-like syndrome is occurring simultaneously. Necrotizing fasciitis develops at the level of the superficial fascia and involves the overlying dermis in most cases?. 24, 37 The diagnosis is often initially confused with cellulitis. When this happens, the patient fails to respond clinically despite appropriate antibiot-

ics. When the dermis is only minimally involved, the extension of the infection to the fascia1 plane is often underestimated or confused with a deep vein thrombosis. In this case, antibiotics are mistakenly withheld at a critical period of time. Muscle and the deep fascia are spared in most cases; however, circumferential infection of a limb can lead to a compartment syndrome, resulting in myonecrosis. In general, the deeper the infection within the skin, the more likely bacteremia and necrosis of skin will occur. Rates of bacteremia as high as 60% have been noted in cases of necrotizing fasciitis due to group A Streptococcus as compared with 10% in cases of cellulitis.19, 38 Thrombosis of the dermal blood supply leads to gangrene of the skin in 35% of casesz4Neuronal loss may leave the skin devoid of sensation. BACTERIOLOGY

With respect to the organisms present, aerobes are found 10%of the time and anaerobes approximately 20% of the time.9 The remaining 70% are mixed with anaerobic and aerobic organism^.^ A single organism is isolated from wound cultures in less than 10% of cases.*5In two large reviews, averages of

From the Departments of Medicine (DRS, SLG), Community Health (SLG), and Molecular Biology (SLG), Tufts University School of Medicine; and the Division of Geographic Medicine/Infectious Diseases (DRS), New England Medical Center; St. Elizabeth's Medical Center (SLG); and the Department of Medicine, Lemuel Shattuck Hospital (DRS), Boston, Massachusetts ~

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3.1 to 4.6 organisms were isolated per culture specimen?,30 The usual aerobic organisms include group A Streptococcus, Staphylococcus aureus, Escherichia coli, and other enterobacteriaceae?, l5 Anaerobic organisms include Peptostreptococcus spp, Prevotella spp, Porphyromonas spp, Fusobacterium spp, Bacteroides spp, and Clostridium Unusual pathogens include group B, C, G, or F Streptococcus, Haemophilus influenzae type b, Pseudomonas aeruginosa, Aeromonas hydrophila, Vibrio vulnifcus, Vibro cholerae, and Flavobacterium odorat~rn.~, 11, 15, 20, 21* 42 On occasion, Rhizopus arrhizus and Mucor may cause disease.z9,45 Polymicrobial infection usually reflects organisms introduced to the skin and soft tissue at the site of trauma or surgery. Mixed infections with S. aureus and other pathogens including Streptococcus pyogenes occur at times; therefore, it is necessary to treat broadly initially and obtain the culture results in order to adjust the therapy. Various aerobic and anaerobic enteric organisms are common in infections originating in the perineum or in the wound following abdominal surgery.

impedes phagocytosis, and both the M protein and the pyogenic exotoxins (A, B, C, SSa, MF) function as superantigens.28,41 Release of these superantigens leads to the liberation of cytokines from activated T cells and a toxic shock-like syndrome. The occurrence of bacteremia, the high mortality, and the frequent absence of desquamation are seen with this toxic-streptococcal syndrome, but not with the well-described staphylococcal toxic shock syndrome. RISK FACTORS FOR DISEASE

In 80% of cases, necrotizing fasciitis is caused by bacteria that extend from localized skin infections or contaminate disruptions of the skin.17 The remainder occur spontaneously or following a bacteremia from another source. Necrotizing fasciitis is rare in children. Most affected children are granulocytopenic 27 secondary to chemotherapy or le~kemia.~, Gram-negative organisms such as P. aeruginosa are frequently isolated. Disease in infants has been associated with fetal scalp monitoring devices and circumcision.', l6 Primary varicella infections have been associated with Group A Streptococcus fasciitis secondary to group A Streptococcus.* Hypotension and renal failure were noted in Approximately 10% of cases of necrotizing fasciitis are caused by group A Streptoc~ccus.~ more than 30% of those infected. Most of these children do well with rapid and aggresIn 1989, Stevens reported 20 patients with sive management. In a review of 14 cases an invasive form of group A streptococcal treated with surgery, all survived.* Twelve infection,4O of whom one quarter had necroof the 14 cases were treated with hyperbaric tizing fasciitis. Shock and renal failure ocoxygen? curred in 80% of those reported; adult respiRisk factors for necrotizing fasciitis in ratory distress syndrome occurred in 55%. adults include a contaminated wound, abraThe mortality in this group reported was sion, or boil. Insect bites or injection sites of 30%. What was striking about this report was intravenous drug users can become infected that 80% of these patients were less than 50 and lead to fasciitis. Preexisting skin condiyears old and 65% had no predisposing illtions such as psoriasis are associated with a ness. This is in contrast to well-known risk higher rate of infection. factors in other forms of necrotizing fasciitis Fasciitis in the perineum (in men, termed such as old age, cancer, or other serious mediFournier's gangrene) originates from a perianal cal problems. In 35% of these new cases, no or ischiorectal abscess, a genitourinary proceobvious portal of entry was identified. Subsedure such as dilation of urethral stricture, quent to this report, others have reported traumatic insertion or removal of a urinary similar cases with mortality as high as catheter, or it can occur spontane~usly.~~ In 70%.'2, 34 The British tabloid press termed the women, infection originating from a Bar"new" disease flesh-eating bacteria following tholin's gland abscess has the potential to cases from Gloucestershire in 1994.2,lo As can develop into fasciitis. be imagined, public awareness has remained Known risk factors include old age, periphhigh following these reports. eral vascular disease, diabetes, renal or liver Most cases of invasive group A Streptococdisease, and alcoholism. Acquired immunocus are M-type 1, 3, 12, or 28, and most prodeficiency syndrome has been associated with duce either exotoxin A or B. The M protein

NECROTIZING FASCIITIS

increased incidence of skin infections in general, some of which develop into fasciitis. In persons with group A streptococcal infections, as many as 50% have no prior medical condition^.^^ There is an association with preexisting streptococcal pharyngitis; 10% of patients with fasciitis due to group A Streptococcus harbor the organism in their throatsM Nosocomial transmission has been well documented with group A Streptococcus.22 Environmental exposure to fresh or brackish water is associated with the development of infections due to Aeromonas hydrophila. Leeches, used medicinally or acquired while swimming, have been associated with severe skin and soft tissue infections with this organism.43Vibrio vulnificus infections occur following exposure to salt water; cirrhosis has been identified as an important risk factor, and most cases are associated with swimming in the Gulf of Mexico or eating shellfish from the warm gulf waters. CLINICAL PRESENTATION Severe local pain is the most common initial symptom in necrotizing fasciitis. The affected area looks slightly red and edematous at first; however, these early signs may be hard to discern. Often, a trivial skin lesion is noted within or close to the area of redness. This may help to distinguish fasciitis from a deep vein thrombosis. Fever is present early in most cases. The tempo of the illness reflects the nature and inoculum of the organisms present in the wound and the general premorbid health of the patient. It has been observed with infections with group A Streptococcus that use of nonsteroidal anti-inflammatory agents suppresses the early symptoms and signs of illness. This can lead to a delay in the initial diagnosis and a poor o ~ t c o m e In . ~ general, signs of erythema, edema, and at times, gangrene, progress slowly over 2 to 4 days. In time, the patient becomes septic, with fever and disorientation. Palpation of the affected area reveals a wooden-hard consistency of the subcutaneous tissues. Crepitance is noted in 30% of cases and is associated with infections caused by’ a number of aerobes and anaerobes including Enterobacteriaceae or CZostridium.3O This is more common in patients with diabetes. With group A streptococci, infection often sp-ads rapidly, with the development of

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Figure 1. Necrotizing fasciitis due to group A Streptococcus in a diabetic foot.

large dark red and violaceous bullae (Fig. 1). Hypotension, renal failure, and adult respiratory distress syndrome occur early in the disease. Fournier’s gangrene begins in the perineum and may initially be overlooked in the evaluation of fever in an elderly, demented man. It often starts as a area of necrosis on the scrotum, and rapidly spreads to the base of the scrotum, perineum, and anterior abdominal wall (Fig. 2). Because of the separate blood supply, the testes do not undergo necrosis. Edema of the penis may rapidly lead to urethral obstruction. DIAGNOSIS The diagnosis of fasciitis is often difficult to make at presentation. Clues include the ability to palpate a hard, wooden feel of the subcutaneous tissues that extends beyond the area of apparent skin involvement, the rapid development of bullae or skin necrosis in the region of presumed cellulitis, crepitance, and the absence of lymphangitis. Failure to respond clinically after 24 to 48 hours of appropriate antibiotics also suggests fasciitis over cellulitis, especially in high-risk patients. Plain radiographic films of the affected site are excellent ways to look for soft tissue gas (Fig. 3). In one small study, all of the patients who were noted to have gas in the soft tissues at surgery had soft tissue gas by radiography. This is compared with only 20% of patients who had evidence of gas by pa1pati0n.l~

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cal exploration, a thin brownish discharge emerges from the wound. Finding pus is rare. A foul odor at exploration is associated with the presence of Bactevoides and other anaero b e ~A. ~blunt probe or finger can be passed in the subcutaneous compartment within the plane between the fascia and dermis. The fascia is dull gray. Culture results from the surgical site are almost always positive. Because anaerobes are the sole pathogens in over 20% of infections, appropriate anaerobic cultures must be obtained at the time of surgery. Gram staining can be helpful in guiding antimicrobial therapy. TREATMENT

Initial resuscitation with fluid replacement and blood pressure support is critical. Extensive surgical debridement (fasciotomy) is the mainstay of effective treatment for necrotizing fasciitis (Fig. 5). On rare occasions, antibiotic therapy alone may be adequate. The decision to go to surgery is made (1) following failure to respond to 24 to 48 hours of parenFigure 2.

Fournier's gangrene.

Magnetic resonance imaging and computed tomographic scanning have been used to distinguish cellulitis from fasciitis. With magnetic resonance imaging, high signal intensity of the fascia in the T2-weighted images 31 strongly suggests fa~ciitis.~, Fine needle aspiration has been used to look for organisms or pus in a suspected area of fasciitis. The sensitivity of this test is indeterminate because no large studies have been done in this setting. The procedure is not adequate for diagnosing the extent or depth of infection. In one study, four out of four aspirations in patients with suspected surgical wound infections yielded pathogens.23 Biopsy with frozen section has been used in order to facilitate an early diagnosis and early treatment in patients with suspected f a ~ c i i t i sIn . ~a~ small study, the delay in diagnosis and surgical treatment was 21 hours in the patients who received biopsy and frozen sections versus 6 days in those who did not have biopsy. The mortality in these two groups was 12.5% versus 72.7%.37 Direct inspection of the fascia is the fastest way to make the diagnosis (Fig. 4). On surgi-

Figure 3. Typical appearance of gas in the soft tissue of the arm.

NECROTIZING FASCIITIS

Figure 4. Appearance of the fascia at surgery

teral antibiotics for presumed cellulitis, (2) when profound toxicity occurs at the onset of infection, (3) when extensive necrosis or gas is noted in the wound or on radiography, and (4) when a compartment syndrome is suspected (Fig. 6). Delay of surgery has been attributed to a number of factors, including

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whether the patient is treated on a medical or a surgical service.8 Incision, blunt dissection, and packing of the wound with wet-to-dry gauze dressing are performed. Counterincisions are made in order to assess spread to sites beyond that which is obviously infected. On occasion, amputation is necessary. Surgical reexploration of the wounds at the bedside or in the operating room is needed almost daily until all necrotic tissue is removed and healing has begun. Antimicrobial therapy is directed toward the results of the initial Gram stain (Table 1). In experimental models, clindamycin is much more effective than penicillin in the treatment of serious group A streptococcal infection^.^^ Clindamycin suppresses both toxin and M protein synthesis. With high concentrations of bacteria, penicillin has been found to lose its effectivene~s.~~ Because of this, when gram-positive bacteria are observed at surgery, a combination of high-dose ceftriaxone and clindamycin is reasonable. Both cover S. auwus, which can be a co-pathogen. In a patient with serious penicillin allergy or in nosocomial infections in hospitals where methacillin-resistant S. uureus (MRSA) is prevalent, empiric therapy with vancomycin and clindamycin should be considered. Mixed gram-negative and gram-positive infections should be treated with drugs such as ticarcillin-clavulanate, ampicillin-sulbactam, or imipenem. An aminoglycoside should be added initially in immunocompromised patients. In neutropenic children antibiotics should include coverage of P. aeruginosa. Hyperbaric oxygen therapy remains con-

Figure 5. Radical fasciotomy of an extremity.

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Suspect necrotizing fasciitis

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Immediate surgery f hyperbaric oxygen

pzl antibiotics

Figure 6. Evaluation of fasciitis. dx

troversial and should never delay antibiotic delivery or surgery. In a 9-year retrospective review, patients with necrotizing fasciitis who received hyperbaric oxygen had no evidence of lower mortality or a decreased number of surgical debridement~.~~ Other studies have refuted these findings?* It is possible that hyperbaric oxygen is beneficial for a subset of patients with necrotizing fasciitis caused by anaerobic gram-negative organisms. To date, however, no prospective studies are available. Anecdotal reports have suggested that intravenous immune globulin (ivIG) is useful in the treatment of toxic streptococcal fasciitis infections." Nutritional therapy is important for wound healingz5High-risk patients including those with liver disease often have preexisting vitamin and nutritional deficits. Consideration for total parenteral nutritional or tube feedings should be given early in the course. PREVENTION

There is no way to prevent sporadic cases of necrotizing fasciitis. Attention must be

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given to all trivial skin infections, especially in patients with diabetes, vascular disease, or a compromised immune status. Careful wound closure (especially when retention sutures are placed following abdominal surgery) is important. Vaccination for chicken pox should decrease the numbers of children who develop fasciitis secondary to superinfection. Nosocomial transmission of group A streptococcal disease has been documented, and all of these cases should be reported to the hospital epidemiologist. Each case needs to be thoroughly investigated. The staff should maintain barrier precautions in all suspected cases. When two or more cases are identified in the same institution, all staff members who have had contact with the patient should be examined for skin infections and pharyngitis. Wound, throat, vaginal, and rectal cultures should be obtained from persons who have been in contact with the index cases.6,26, 33 Streptococcal carriers are sent home and treated. Rifampin has been effective for treatment of oral and vaginal carriers. Oral vancomycin is effective for rectal carriers. There is no consensus as to the duration of therapy,

Table 1. ANTIBIOTICS FOR FASCllTlS Organism Group A Streptococcus

Staphy/&occus aureus Mixed infections

Initial Consideration Ceftriaxone and clindamycin or penicillin and clindamycin Nafcillin or oxacillin Irnipenern/cilastatin,ticarcillinlclavulanate, piperacillinhazobactarn, ampicillin/ sulbactam, and aminoglycoside

Penicillin allergy Vancornycin and clindamycin Vancornycin Vancornycin and clindarnycin and ciprofloxacin

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but employees should be culture-negative prior to returning to work. Temporary closure of the operating rooms may be necessary in order to investigate an outbreak. SUMMARY Necrotizing fasciitis, by nature of its high inoculum of aggressive bacteria and the depth of the fascia1 involvement, is one of the most serious infections known to humans. Rapid tissue destruction of skin and fascia, along with bacteremia, is common. The mortality for this disease is much higher than that for cellulitis. Unfortunately, delay in diagnosis occurs commonly. The emergence of toxic shock strains of Streptococcus leading to fasciitis with organ dysfunction makes it necessary to make a rapid diagnosis and institute early antibiotic and surgical interventions.

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35. Shupak A, Shoshani 0, Goldenberg I, et al: Necrotizing fasciitis: An indication for hyperbaric oxygen therapy? Surgery 118:873-878, 1995 36. Spimak JP, Resnick MI, Hampel N, et a1 Foumier’s gangrene: Report of 20 patients. J Urol 131:289-291, 1984 37. Stamenkovic I, Lew P D Early recognition of potentially fatal necrotizing fasciitis. N Engl J Med 310~1689-1693,1984 38. Stevens D L Streptococcal toxic-shock syndrome: Spectrum of disease, pathogenesis, and new concepts in treatment. Emerging Infectious Diseases 1:69-78, 1995 39. Stevens DL, Gibbons AE, Bergstrom R, et al: The Eagle Effect revisited: Efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis 158:23-28, 1988 40. Stevens DL, Tanner MH, Winship J, et al: Severe Group A streptococcal infections associated with a

toxic shock-like syndrome and scarlet fever toxin A. N Engl J Med 321:l-7,1989 41. Tomai M, Kotb M, Majumdar G, et a1 Superantigenicity of streptococcal M protein. J Exp Med 172:359362, 1990 42. Wagner PD, Evans SD, Dunlap J, et al: Necrotizing fasciitis and septic shock caused by Vibrio cholerue acquired in San Diego, California. West J Med 163:375-377, 1995 43. Wilken GB, Appleton CC: Bacteriological investigation of the occurrence and antibiotic sensitivities of the gut-flora of the potential southern African medicinal leech, Asiaticobdellu buntonesis (Hirudinidae). J Hosp Infect 23:223-228, 1993 44. Wilson CB: Necrotizing fasciitis. Am Surg 18416, 1952 45. Wilson CB, Siver GR, OBrien GF, et al: Phycomycotic gangrenous cellulitis. Arch Surg 111:532, 1976 46. Yong JM: Necrotizing fasciitis [letter]. Lancet 343:1427, 1994

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