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Vol 8, No 3, May/June 2000 151 Necrotizing soft-tissue infections have been recognized for centuries. Hippocrates vividly described the disease in the 5th century BC, as fol- lows: ÒThe erysipelas would quickly spread in all directions. Flesh, sinews, and bones fell away in great quantities.Ó Necrotizing soft-tissue infections were subsequently designated as Òstreptococcal gangrene,Ó Òphage- dena,Ó and Òphagedena gangreno- sum.Ó The first report of necrotizing fasciitis in the United States was made in 1871 by Joseph Jones, 1 a Confederate Army surgeon, who called it Òhospital gangreneÓ and described it thus: ÒI have seen the skin in the affected spot melt away in twenty-four hours into a grayish and greenish slough.Ó By the early 1900s, hospital gangrene was believed to be a disease of the past. However, sporadic outbreaks were still reported. In 1924, Meleney 2 described an outbreak of Òhemolytic streptococcal gangreneÓ in a Peking hospital. In this report, he emphasized the critical role of early surgical debridement. The term Ònecrotizing fasciitis,Ó as it is commonly designated today, first appeared in a report by Wilson 3 in 1952 and perhaps best describes the key aspect of the infectious process. Sporadic outbreaks continue to be reported and have piqued the inter- est of the popular press. When a cluster of cases were reported in Gloucestershire, England, in 1994, the British tabloids termed this ÒnewÓ disease Ògalloping gangreneÓ and referred to the cause as a Òkiller bugÓ and Òflesh-eating bacteria.Ó These sensationalistic descriptions, and the fact that this disease can strike healthy young individuals and cause devastating morbidity and mortality in a matter of hours, have led to widespread concern about necrotizing fasciitis in the general public. While there is no consensus among infectious disease and epi- demiology experts, there are a few reports documenting an increasing incidence of necrotizing fasciitis. For example, in Sweden, the incidence of group A streptococcal bacteremia increased from 1.8 per 100,000 in 1987 to 2.4 per 100,000 in 1989. 4 However, other authors believe that the numerical increase is due to heightened awareness and better reporting, rather than reflect- ing a true increase in incidence. While there has been no active sur- veillance of group A streptococcal Dr. Fontes is Assistant Professor of Ortho- pedic Surgery, University of California, San Francisco. Dr. Ogilvie is Resident, Depart- ment of Orthopedic Surgery, University of California, San Francisco. Dr. Miclau is Assistant Professor of Orthopedic Surgery, University of California, San Francisco. Reprint requests: Dr. Fontes, Department of Orthopedic Surgery, San Francisco General Hospital, Room 3A36, 1001 Potrero Avenue, San Francisco, CA 94110. Copyright 2000 by the American Academy of Orthopaedic Surgeons. Abstract Necrotizing fasciitis is a rare and often fatal soft-tissue infection involving the superficial fascial layers of the extremities, abdomen, or perineum. Necrotizing fasciitis typically begins with trauma; however, the inciting event may be as seemingly innocuous as a simple contusion, minor burn, or insect bite. Differentiating necrotizing infections from common soft-tissue infections, such as cellulitis and impetigo, is both challenging and critically important. A high degree of suspicion may be the most important aid in early diagnosis. Prompt diagnosis is imperative because necrotizing infections typically spread rapidly and can result in multiple-organ failure, adult respiratory distress syndrome, and death. Although group A Streptococcus is the most common bacterial iso- late, a polymicrobial infection with a variety of Gram-positive, Gram-negative, aerobic, and anaerobic bacteria is more common. Orthopaedic surgeons are often the first physicians to evaluate patients with such infections and therefore need to be familiar with this potentially devastating disease and its management. Prompt diagnosis, immediate administration of broad-spectrum antibiotic coverage, and emergent aggressive surgical debridement of all compromised tissues are critical to reduce the morbidity and mortality of these rapidly pro- gressing infections. J Am Acad Orthop Surg 2000;8:151-158 Necrotizing Soft-Tissue Infections Roger A. Fontes, Jr, MD, Christian M. Ogilvie, MD, and Theodore Miclau, MD Necrotizing Soft-Tissue Infections Journal of the American Academy of Orthopaedic Surgeons 152 infections in the United States, the incidence of infections between 1989 and 1991 has been estimated to be between 10,000 and 15,000 cases annually. Of these, approxi- mately 5% to 10% were necrotizing infections, with a mortality rate of 28%. 5 Fortunately, necrotizing infections are rare complications of orthopaedic surgery. However, a recent report detailing the deaths of three young, previously healthy individuals after minor musculo- skeletal trauma 6 underscores the devastating impact of this disease. Clinical Presentation Soft-tissue infections encompass a wide spectrum of disease entities, ranging from the superficial to the deep and from the merely inconve- nient to the life-threatening (Fig. 1). Early clinical findings of necrotizing soft-tissue infection may be limited to pain, mild swelling, and redness. At this stage, differentiating necrotizing fasciitis from cellulitis or another superficial soft-tissue infection may be impossible. However, serial examinations will show a failure to respond to antibiotics appro- priate for cellulitis (Fig. 2). Systemic signs of sepsis may become apparent, including hypotension, acidosis, leukocytosis, tachycardia, hyper- thermia, or, even more worrisome, hypothermia. The treating surgeon may find that a patient admitted with a diagnosis of cellulitis only 12 to 48 hours earlier has become critically ill, requiring blood pressure support because of multiple-organ failure. In most cases, necrotizing fasciitis is caused by bacteria arising from a localized skin infection or contaminated wound. Severe local pain is the most common initial symptom. Fever is typically present in the early stages. Frequent early physical examination findings are local tenderness and mild erythema with edema. Subcutaneous crepitation may also be present. The area of localized tenderness is often associated with an almost trivial skin lesion; the presence of this finding should be meticulously evaluated when the physical examination is performed. The progression of necrotizing soft-tissue infection is variable, de- pending on the size of the bacterial inoculum, the organism involved, the location of the infection, and the health status of the patient. Rates of bacteremia as high as 60% have been noted in necrotizing fasciitis. 7 A single organism is isolated from wound cultures in only 10% of cases. The average number of organisms isolated ranges from 3.1 to 4.6. 8 Necrotizing infections are more common and tend to progress more rapidly in persons who have compromised immune systems and underlying medical problems, such as diabetes mellitus, intravenous drug use, liver disease, alcoholism, or chronic illness. Local soft-tissue conditions likely also play an important, but not well-described, role in resisting infection. For example, the tissue hypoxia that is present in postsurgical or postradiation wounds and in the extensive cutaneous scars noted in many intravenous drug abusers may contribute to decreased resistance to infection in these types of wounds. In general, edema, erythema, and, at times, necrosis progress slowly over Figure 1 Cross-sectional diagram of the skin and subcutaneous tissue showing the typical location of various soft-tissue infections. (Adapted with permission from Green R, Dafoe D, Raffin T: Necrotizing fasciitis. Chest 1996;110:219-229.) Epidermis Location Disorder Dermis Superficial fascia Subcutaneous fat, nerves, arteries, veins Deep fascia Muscle Necrotizing fasciitis Myonecrosis (clostridial and nonclostridial) Cellulitis Erysipelas Impetigo Folliculitis Ecthyma Furunculosis Carbunculosis Figure 2 Typical appearance of necrotizing fasciitis before debridement. Erythema and a small skin lesion are visible. Roger A. Fontes, Jr, MD, et al Vol 8, No 3, May/June 2000 153 2 to 4 days. However, group A streptococcal infections often spread very rapidly, with the development of dark red bullae. Adult respiratory distress syndrome (ARDS), renal failure, and hypotension may occur quite early in the disease course. Dividing necrotizing soft-tissue infections into different entities is generally not useful because the diagnostic and treatment regimens are the same. Several authors, including Elliott et al, 9 feel that pure clostridial myonecrosis is the only such infection that needs to be separately distinguished because of its nearly uniform muscle involvement and its higher mortality rate. This condition can present like other necrotizing infections but has some characteristic findings, including bronze-brown skin discoloration, edema, bullae, and copious drain- age. The triad of pain, tachycardia out of proportion to fever, and crepitus suggests clostridial myonecrosis but does not exclude another necrotizing soft-tissue infection. The course of clostridial myonecrosis can be rapid: the incubation period is commonly 24 hours or less, which is shorter than the 3 to 4 days typical for streptococcal myositis. Radiography reveals gas in the muscle bellies more often than with other gas-forming infections. 10 Radiologic Evaluation Radiographic evaluation is not nor- mally indicated in the workup of soft-tissue infections, but can be helpful if air is seen in the soft tissues (Fig. 3). While subcutaneous air can be seen in less rapidly ad- vancing soft-tissue infections, such as diabetic foot infections, it is also characteristic of more aggressive necrotizing soft-tissue infections. Rates of the presence of subcutaneous air in patients with necrotizing fasciitis have ranged from 24% to 73% in different series. Computed tomography may be even more sensitive than plain radiography for detecting air in the soft tissues. 11 While anaerobic infection should be strongly suspected if subcutaneous air is detected, aerobic infection can produce subcutaneous air, particularly in diabetic persons and patients with severe peripheral vascular disease. Magnetic resonance imaging has been evaluated as a tool for differentiating cellulitis from necrotizing fasciitis, which is a very useful clinical distinction. In a study of 33 patients with cellulitis and surgi- cally proven necrotizing fasciitis, this study allowed differentiation of cellulitis from necrotizing infections in all cases. 12 The investiga- tors found that while both cellulitis and necrotizing fasciitis are characterized by decreased T1 and increased T2 signal in subcutaneous fat, only necrotizing fasciitis demonstrates increased T2 signal in the fascia itself (Fig. 4). Laboratory Evaluation Laboratory evaluation should include a complete blood cell count, serum albumin determination, elec- trolyte panel (including calcium, creatinine, and blood urea nitrogen), liver function tests, prothrombin time, and partial thromboplastin time. The results obtained will reflect the status of the infection: early in the course, few abnormalities may be identified; if septicemia and multiple- organ failure subsequently develop, this will be reflected in the laboratory values. Figure 3 A, Anteroposterior radiograph of the upper extremity shows extensive subcutaneous air in a patient with necrotizing fasciitis. B, Oblique radiograph better demonstrates the extent of subcutaneous air. A B Necrotizing Soft-Tissue Infections Journal of the American Academy of Orthopaedic Surgeons 154 In addition to diagnostic value, the laboratory evaluation may also have predictive value regarding the severity of the infection. Elliott et al 9 found that certain laboratory abnormalities, such as decreased platelet count and elevated blood urea nitrogen, creatinine, bilirubin, and blood lactate levels, were associated with death in the 198 cases reviewed (Table 1). Mortality Mortality rates, which have ranged from 23% to as high as 76%, have changed little once the need for early surgical intervention was recognized in 1924 by Meleney. 2 A recent meta-analysis of 14 studies with a total of 660 patients revealed an overall mortality rate of 26%. 13 Risk factors for increased mortality include advanced age, diabetes mellitus, peripheral vascular disease, poor nutrition, immunocompro- mise, obesity and intravenous drug abuse. Infections of the trunk and perineum were associated with the highest mortality rates. The cause of death in most cases is multiple- organ failure, ARDS, or overwhelm- ing sepsis. In general, deaths that occur within 10 days of initial debridement are caused by sepsis, whereas later deaths are due to multiple-organ failure. 6,13-15 Histopathology The characteristic histologic findings in necrotizing fasciitis are necrosis of the superficial fascia with blood ves- sel thrombosis and suppuration. Other findings may include necrosis of the superficial fat and overlying dermis, vasculitis, and local hemor- rhage (Fig. 5). The presence of inflammatory cells distinguishes necrotizing fasciitis from infections like clostridial myonecrosis. 10 In a retrospective review of the data on 19 patients with necrotizing fasciitis, Stamenkovic and Lew 16 demonstrated that frozen-section biopsy may be useful for early diag- Figure 4 Necrotizing fasciitis in a 3-year-old girl after an insect bite to her posterolateral right thigh. T1-weighted (A) and T2-weighted (B) images show a normal left thigh and hyperintense signal intensity in the superficial and deep fascia of the right thigh. Surgical findings included fascial necrosis. (Courtesy of Eliana D. Delgado, MD, San Francisco.) A B Table 1 Mean Admission Laboratory Values in Study by Elliott et al 9 All Patients Survivors Nonsurvivors N Mean N Mean N Mean P Measurement Value Value Value Value Hemoglobin, g/dL 195 11.5 147 11.7 48 10.8 0.03 Leukocyte count, 1,000/mm 3 198 18.1 148 18.0 50 18.4 0.83 Platelet count, 1,000/mm 3 191 300 145 325 46 222 <0.001 Urea nitrogen, mg/dL 193 34.4 145 27.7 48 54.4 <0.001 Creatinine, mg/dL 193 2.1 145 1.8 48 3.1 <0.001 Total bilirubin, mg/dL 168 1.5 126 1.2 42 2.6 <0.001 Serum calcium, mg/dL 182 8.1 136 8.2 46 7.8 0.01 Serum albumin, g/dL 152 2.2 113 2.3 39 2.2 0.55 Blood lactate, % above normal 153 81.1 109 22.4 44 226 <0.001 Prothrombin time, sec 179 13.7 135 13.2 44 15.1 0.001 * Adapted with permission from Elliott DC, Kufera JA, Myers RA: Necrotizing soft-tissue infections: Risk factors for mortality and strategies for management. Ann Surg 1996;224:672-683. Vol 8, No 3, May/June 2000 155 nosis. Eight patients underwent frozen-section biopsy, which pro- vided confirmation of the diagnosis and allowed early surgical debridement to be performed an average of 21 hours after presentation. Only 1 patient in this group died. In the cases of 11 patients who did not undergo a frozen-section biopsy, the time to diagnosis and surgical debridement averaged 6 days. Eight (74%) of these patients died, 6 of them because of progression of fasciitis and sepsis. The surgical debridement was judged to be more extensive in the group who did not undergo frozen-section biopsy. The authors concluded that early diagnosis reduced morbidity and mortality, and that frozen-section biopsy was confirmatory of the diagnosis in all cases in which it was used. Microbiology No single organism is responsible for the fascial necrosis and systemic toxicity seen in necrotizing fasciitis: aer- obes, anaerobes, and Gram-negative and Gram-positive bacteria have all been isolated from necrotizing infections. Although infections with a single isolated organism are not infrequent, the synergistic action of multiple organisms has been impli- cated in the fascial necrosis and systemic toxicity. Necrotizing fasciitis has been divided into distinct groups on the basis of bacterial culture results. Type I is a polymicrobial infection that typically involves the trunk and generally results from surgical wound complications. Bacterial species in these infections include nonÐgroup A streptococci and both nonfacultative and facultative anaerobes. In type II disease, the pathogens are group A streptococci, with or without staphylococci. This type of infection more typically af- fects the extremities. A third type of necrotizing infection is caused by the marine vibrios (Gram-negative rods), including Vibrio vulnificus, V parahaemolyticus, V damsela, and V alginolyticus. The typical portal of entry is a puncture wound, cut, abrasion, or insect bite exposed to seawater or marine ani- mals. The pathogenic vibrios are believed to synthesize an extracellular toxin that destroys the soft tissues. Group A streptococci produce many constituents that contribute to their pathogenicity. First, sur- face proteins that inhibit phagocytosis, in particular M protein, are expressed. It should be noted that there are many different subtypes of M protein, and some species do not produce this protein at all. Most strains of group A streptococci involved in streptococcal toxic shock syndrome produce subtypes 1 and 3. Probably even more significant than M protein are the extracellular protein products secreted by group A streptococci. Streptococcal pyrogenic exotoxins (SPEs) have been characterized as types A, B, and C. Roger A. Fontes, Jr, MD, et al Figure 5 Left, Debridement specimen from the lower leg of a patient with necrotizing fasciitis demonstrates necrotic muscle (arrow), adjacent necrotic fascia (arrowheads), and thrombosed vessels and inflammatory cells (aster- isks)(hematoxylin-eosin, original magnification ×4). Above, Higher-magnification view of another region of same specimen shows necrotic fascia with extravasated red blood cells (asterisk) and diffuse distribution of inflammatory cells (arrows)(hematoxylin-eosin, original magnification ×10). Necrotizing Soft-Tissue Infections Journal of the American Academy of Orthopaedic Surgeons 156 These toxins have been shown in experimental models to induce a cytotoxic response, initiating shock- like symptoms. Interestingly, SPE type A and staphylococcal toxic shock syndrome toxin 1 have simi- lar molecular structures. The exact pathologic process that is initiated and propagated by the SPEs is not well understood. It is known that SPE type B is a cysteine protease. Streptococcal pyrogenic exotoxins increase their pathogenicity and act as ÒsuperantigensÓ by stimulat- ing a massive proliferation of T cells, which in turn produce a cas- cade of cytokines, including tumor necrosis factor and a number of interleukins. These cytokines in turn contribute to the fever, shock, and tissue injury seen in necrotizing fasciitis. There has been some speculation that more virulent strains of group A streptococci have evolved, resulting in the apparent increase in the number and severity of necrotizing infections. Treatment Initial resuscitation with fluid replacement and blood pressure support is critical. Affected patients are often critically ill at presentation or will quickly become so; early involvement of the critical care specialist and/or general surgeon is extremely important. The primary treatment for this disease is complete surgical debridement of all involved tissues (Fig. 6). Necrotizing fasciitis often involves extensive fascial tissue loss beyond the apparent superficial borders of the infection due to rapidly ad- vancing necrosis. Repeat debridement is the rule rather than the ex- ception. Intravenous antibiotics should be administered in conjunction with surgical debridement. Although antibiotics have a minimal effect on the wound itself, they reduce the bacterial load and may decrease the incidence of organ failure. Antibi- otic coverage should be tailored to the organisms involved in the particular infection. The initial Gram stain can be useful in selecting the antibiotic regimen. Clindamycin has been shown experimentally to be more effective than penicillin against Streptococcus. 17 This is probably due to a variety of factors, including a relatively lower expres- sion of penicillin binding in rapidly progressive infections. Clindamy- cin may be the most efficient antibiotic because it is not affected by inoculum size, and it inhibits protein production (including the exotoxins and M proteins that block phagocytosis). Combination therapy with ceftriaxone or vancomycin to cover possible concomitant staphylococcal infection is warranted. Patients with wounds that have subcutaneous gas or Gram-negative organisms should be treated with a wide-spectrum antibiotic, such as imipenem or ticarcillin-clavulanate, combined with aminoglycosides if renal function has not been compromised. While the mainstays of treatment for necrotizing infections have been in place for a number of years, alternative and adjunc- tive treatment modalities have recently been investigated. These include the use of intravenous immunoglobulin and hyperbaric oxygen. The finding that SPEs act as superantigens has led to the investi- gation of intravenous administration of human immunoglobulin in the management of severe streptococcal infections. A recent clinical and laboratory study involving patients with streptococcal toxic shock syndrome showed a 40% drop in the mortality rate in those treated with human immunoglobulin compared with the control group. The current recommended dosage is 2 g per kilogram of body weight daily for 2 days. Hyperbaric oxygen treatment has also been explored. In a 9-year retrospective review, Riseman et al 15 found that hyperbaric oxygen therapy significantly reduced (P<0.05) mortality due to necrotizing infections, with a mortality rate of 23% in treated patients, compared with 67% in the group of patients who did not receive such therapy. An- other study reached the opposite conclusion, although there was a decrease in mortality in the treated group. 14 Unfortunately, no prospective study has demonstrated the benefit of either intravenous human immunoglobulin or hyperbaric oxygen therapy. Therefore, while uncer- tainty persists regarding the efficacy of these therapeutic modalities, the current consensus is that their administration certainly should not delay definitive surgical and medical treatment. Figure 6 Necrotizing fasciitis of the del- toid region after serial debridements. Vol 8, No 3, May/June 2000 157 References 1. Jones J: Observations upon the losses of the Confederate armies from battle, wounds and disease during the American Civil War of 1861-1865, with investigations upon the number and character of diseases supervening upon gun shot wounds. Richmond Louisville Med J 1871;9:453-480. 2. Meleney FL: Hemolytic streptococcus gangrene. Arch Surg 1924;9:317-364. 3. Wilson B: Necrotizing fasciitis. Am Surg 1952;18:416-431. 4. Stromberg A, Romanus V, Burman LG: Outbreak of group A streptococcal bacteremia in Sweden: An epidemio- logic and clinical study. J Infect Dis 1991;164:595-598. 5. Centers for Disease Control and Prevention: Invasive group A streptococcal infections: United KingdomÑ 1994. MMWR Morb Mortal Wkly Rep 1994;43:401-402. 6. Mills WJ, Swiontkowski MF: Fatal group A streptococcal infection with toxic shock syndrome: Complicating minor orthopedic trauma. J Orthop Trauma 1996;10:149-155. 7. Stevens DL: Streptococcal toxic-shock syndrome: Spectrum of disease, patho- genesis and new concepts in treatment. Emerg Infect Dis 1995;1:69-78. 8. Giuliano A, Lewis F Jr, Hadley K, Blaisdell FW: Bacteriology of necrotizing fasciitis. Am J Surg 1977;134:52-57. 9. Elliott DC, Kufera JA, Myers RA: Necrotizing soft-tissue infections: Risk factors for mortality and strategies for management. Ann Surg 1996;224: 672-683. 10. Chapnick EK, Abter EI: Necrotizing soft-tissue infections. Infect Dis Clin North Am 1996;10:835-855. 11. Beauchamp NJ Jr, Scott WW Jr, Gottlieb LM, Fishman EK: CT evaluation of soft tissue and muscle infection and inflammation: A systematic com- partmental approach. Skeletal Radiol 1995;24:317-324. 12. Rahmouni A, Chosidow O, Mathieu D, et al: MR imaging in acute infectious cellulitis. Radiology 1994;192:493-496. Experience at San Francisco General Hospital A retrospective chart review of necrotizing soft-tissue infections of the extremities at San Francisco General Hospital between 1993 and 1997 was performed. A total of 150 infections in 149 patients were identified on the basis of descriptions of necrotic fascia in surgical or pathology reports. (One female patient suffered two necrotizing infections 13 months apart; these were considered separately.) Necrotizing infections occurred in 96 men and 53 women with a mean age of 41.5 years (range, 23 to 77 years). Illicit injectable drugs were involved in 116 cases. Twenty- two patients were identified as human immunodeficiency virusÐ positive; however, not all patients were tested or had test results avail- able for review. Thirteen patients were diabetic, and 3 had known peripheral vascular disease. The findings at the initial evaluation are shown in Table 2. Initial debridement was performed within 24 hours in 87% of the 150 cases. An average of 6.8 days elapsed from the initial symptoms to the first surgical debridement. Additional debridements were carried out in 72% of the cases. The average number of debridements was 2.6. Amputation was performed in 9 cases. The mortality rate was 9.3%, significantly lower (P<0.05) than the 26% reported in a meta-analysis of the data on 660 patients in 14 studies. 13 Summary Necrotizing fasciitis is an uncommon infection of the superficial fascia, which is typically caused by virulent, toxin-producing bacteria. These infections generally involve local wound necrosis and may or may not be associated with severe systemic toxicity, such as that which occurs in shock, ARDS, and end-stage organ failure. Group A streptococci are the most common isolates, but most infections are polymicrobial and may include a mix of aerobic and anaerobic bacteria. A high index of suspicion is needed to identify this infection, which can mimic cellulitis in its early stages. Prompt diagnosis and aggressive surgical debridement are critical to reduce morbidity and mortality. The primary treatment is complete surgical excision of the infected or necrotic tissue. General surgery and/or critical care special- ists should be involved early to assist with the management of these critically ill patients. Antibi- otic therapy should provide broad coverage of both anaerobic and aerobic organisms. Clindamycin has been shown to be the most effective against streptococcal species. Adju- vant therapies, such as intravenous immunoglobulin and hyperbaric oxygen, may have a role in treatment, but studies supporting their use are limited at this time. Roger A. Fontes, Jr, MD, et al Table 2 Initial Evaluation Findings in 150 Cases of Necrotizing Soft-Tissue Infection Treated at San Francisco General Hospital, 1993Ð1997 Finding No. of Cases (%) Erythema 142 (95) Pain 136 (91) Edema 97 (65) Induration 94 (63) Fluctuance 67 (45) Fever 53 (35) Crepitus 8 (5) Bullae 6 (4) Soft-tissue gas on radiography 22 (15) Necrotizing Soft-Tissue Infections Journal of the American Academy of Orthopaedic Surgeons 158 13. Callahan TE, Schecter WP, Horn JK: Necrotizing soft tissue infection mas- querading as cutaneous abscess fol- lowing illicit drug injection. Arch Surg 1998;133:812-818. 14. Brown DR, Davis NL, Lepawsky M, Cunningham J, Kortbeck J: A multi- center review of the treatment of major truncal necrotizing infections with and without hyperbaric oxygen therapy. Am J Surg 1994;167:485-489. 15. Riseman JA, Zamboni WA, Curtis A, Graham DR, Konrad HR, Ross DS: Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. Surgery 1990;108:847-850. 16. Stamenkovic I, Lew PD: Early recogni- tion of potentially fatal necrotizing fasciitis: The use of frozen-section biopsy. N Engl J Med 1984;310:1689-1693. 17. Stevens DL, Gibbons AE, Bergstrom R, Winn V: The Eagle effect revisited: Efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis 1988;158:23-28.