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Review ArticleNecrotizing Fasciitis: Diagnostic Challenges andCurrent Practices

Abhishek Vijayakumar, Rajeev Pullagura, and Durganna Thimmappa

Department of General Surgery, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore,Karnataka 560002, India

Correspondence should be addressed to Abhishek Vijayakumar; [email protected]

Received 12 November 2013; Accepted 5 December 2013; Published 22 January 2014

Academic Editors: E. Ciftci and R. Favory

Copyright © 2014 Abhishek Vijayakumar et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Necrotizing fasciitis or necrotizing soft-tissue infections (NSTIs) are infrequent but highly lethal infections. They can be definedas infections of any of the layers within the soft tissue compartment (dermis, subcutaneous tissue, superficial fascia, deep fascia, ormuscle) that are associated with necrotizing changes. At onset, necrotizing fasciitis can be difficult to differentiate from cellulitisand other superficial infections of the skin. In fact, only 15% to 34% of patients with necrotizing fasciitis have an accurate admittingdiagnosis. Early diagnosis and management with surgical debridement, antimicrobials, and supportive measures reduce mortality.Even with modern ICU care mortality ranges between 16 and 36%; this is related to delays in diagnosis and comorbidities. Variousscoring systems have been developed which help in diagnosis and stratifying patients into risk groups. The present review dealswith varied presentation, early diagnosis, and management of necrotizing fasciitis.

1. Introduction

Necrotizing fasciitis (NF) or necrotizing soft-tissue infections(NSTIs) are infrequent but highly lethal infections. Theycan be defined as infections of any of the layers withinthe soft tissue compartment (dermis, subcutaneous tissue,superficial fascia, deep fascia, or muscle) that are associatedwith necrotizing changes. NSTIs are typically not associatedwith abscesses, although they can originate from an untreatedor inadequately drained abscess. These infections were firstdescribed by Jones [1] in 1871 and at the time were termed“hospital gangrene” that had amortality of 46%. Shortly after-wards, Jean-Alfred Fournier [2] described a type of soft tissueinfection affecting the male perineal region, now known asFournier’s gangrene. This definition has been expandedrecently to include necrotizing infections of the perineum ofmen and women. Surgical debridement was first performedbyMeleney [3] in the early 1920s and has remained an integralpart of current treatment. In 1951, Wilson [4] coined the term“necrotizing fasciitis” to encompass some of these infections.

At onset, necrotizing fasciitis can be difficult to differ-entiate from cellulitis and other superficial infections of theskin. In fact, studies have shown that only 15% to 34% of

patients with NF have an accurate admitting diagnosis [5, 6].Only early diagnosis and aggressive surgical treatment canreduce mortality and morbidity. Family physicians are oftenthe first point of contact for these patients, and a high index ofsuspicion is needed, as there is a paucity of initial signs. Thecurrent review deals with presentation, early diagnosis, andmanagement of necrotizing fasciitis.

2. Classification

There is a great deal of confusion surrounding the identifica-tion anddefinition of necrotizing fasciitis.Historically, necro-tizing infections were classified according to anatomical sites.Fournier’s gangrene (involving the perineum) and Ludwigangina (involving submandibular and sublingual spaces) andMeleney synergistic gangrene (involving abdominal wall) areexamples. These infections were named after the physicianswho first described them.

In 1972 Baxter [7] divided soft tissue infections into threecategories based on surgical management (Table 1).

Lewis [8] proposed an alternate classification system thatgrouped NSTIs into three anatomic categories (Table 2).

Hindawi Publishing CorporationISRN Infectious DiseasesVolume 2014, Article ID 208072, 8 pageshttp://dx.doi.org/10.1155/2014/208072

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Table 1: Classification of soft tissue infections based on treatmentmodality according to Baxter.

Surgical lesions requiring radical incision and drainageAcute streptococcal hemolytic gangreneNecrotizing fasciitisStreptococcal myositisClostridial cellulitisGram-negative anaerobic cutaneous gangrene

Surgical infections requiring excision of tissueProgressive bacterial synergistic gangreneNonclostridial gas-producing infectionsNonclostridial myositisHuman bite infections

Nonoperative infectionsErysipelasLymphangitis and lymphadenitisPurpura fulminans

Table 2: Classification of soft tissue infections by Lewis.

Infections of skin and subcutaneous tissueProgressive synergistic bacterial gangreneChronic undermining burrowing ulcer (Meleney’s ulcer)Idiopathic scrotal gangrene (Fournier’s gangrene)

Infections involving subcutaneous tissue and fasciaHemolytic streptococcal gangreneNecrotizing fasciitisGram-negative synergistic necrotizing cellulitisClostridial cellulitis

Infections involving muscleClostridial myonecrosisStreptococcal myositis

Another classification of necrotizing fasciitis into type 1and type 2 based on microbial cause is used (Table 3).

3. Risk Factors

The precise origin of necrotizing fasciitis is often unclear.Introduction of the pathogenic agent or agents can occur asa result of minor trauma, insect bite, or surgical incision.Hematogenous spread from distal sites of infection has alsobeen reported [9]. Other potential sources include odon-togenic infections [10], varicella lesions [11], intramuscularinjections [12], and contusions [13]. Some cases of NF occurin the absence of any apparent prior trauma [14]. Various riskfactors have been identified in development of NF (Table 4).

Nonsteroidal anti-inflammatory drug use has been impli-cated in severe necrotizing streptococcal infections. It ispostulated that nonsteroidal anti-inflammatory drugs impairlymphocyte function [15]. However, it could also be that sup-pression of symptoms and signs of inflammation leads to laterdiagnosis, especially in patients presenting earlywith nonspe-cific symptoms [16].

Table 3: Classification of necrotizing fasciitis based on microbiol-ogy.

Type 1Polymicrobial infections including anaerobes

Type 2Streptococcus pyogenes (Group A Streptococcus)Staphylococcus aureus, including methicillin-sensitive andresistant

Other microbiological etiologiesVibrio vulnificusAeromonas hydrophilaEnterobacteriaceae (Escherichia coli, Pseudomonas spp., andKlebsiella spp.)

Table 4: Risk factors for necrotizing fasciitis.

Age greater than 50 yearsAtherosclerosisBurnsCancer or otherImmunocompromised stateChronic alcoholismCorticosteroid useDiabetes mellitusHypoalbuminemiaIntravenous drug abuseMalnutritionObesityOccult diverticulitisPeripheral vascular diseasePostoperative infectionTrauma

4. Etiology

Although necrotizing soft tissue infections can be monomi-crobial, they usually are synergistic polymicrobial infections.In an analysis of wound and blood cultures, blood cultureswith a single organism, multiple organisms, and no organismwere found in 27%, 2%, and 71% of cases, respectively. Forthe wound cultures, a single organism, multiple organisms,and no organism were found in 53%, 23%, and 23% of cases,respectively [17].

In a study by Elliott et al. [18] it was found that only 28of 182 patients developed necrotizing skin infections fromsingle pathogens; the other 154 patients had polymicrobialinfections (average of 4.4 organisms in the original woundcultures). In this series, the majority of monomicrobialinfections were caused by streptococcal isolates such asbeta-hemolytic streptococci (namely, Group A streptococcior Streptococcus pyogenes). Other common monomicro-bial necrotizing soft tissue infections include Staphylococcusaureus and Clostridium perfringens.

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Table 5: Clinical features of necrotizing fasciitis.

Skin Pain GeneralErythema with ill-defined margins Pain that extends past margin of apparent infection Fever with toxic appearanceTense edema with grayish or browndischarge Severe pain that appears disproportionate to physical findings Altered mental state

Lack of lymphangitis or lymphadenopathy Decreased pain or anesthesia at apparent site of infection TachycardiaVesicles or bullae, hemorrhagic bullae Tachypnea due to acidosisNecrosis Dehydration

Crepitus Decreased urine outputPresentation with diabeticketo acidosis

The organisms most common in polymicrobial necrotiz-ing soft tissue infections are combinations of staphylococci(especially Staphylococcus epidermidis with beta-hemolyticstreptococci), enterococci, Enterobacteriaceae species (com-monly Escherichia coli, Proteus mirabilis, Klebsiella pneu-moniae, and Pseudomonas aeruginosa), streptococci, Bac-teroides/Prevotella species, anaerobic gram-positive cocci,and Clostridium species [19].

5. Clinical Presentation

Necrotizing infections can occur anywhere in the body,although some anatomic locations are affected more com-monly. Most necrotizing soft tissue infections occur in theextremities, abdomen, groin, and perineum. In a case series,these infections were discovered in the extremities (53 per-cent of cases), perineum or buttocks (20 percent), trunk (18percent), and head and neck (8.9 percent) [20].

As NF first starts in the deep tissue planes, at initialpresentation theremight beminimal epidermal involvement.This canmake it difficult to differentiate from nonnecrotizingskin infections and cellulitis. Also minor trauma whichpresents as cellulitis may have deeper plane extension andmay initially be missed. Patients with NF are usually system-ically toxic, presenting with fever (temperature greater than38∘C), tachycardia, diaphoresis, and even an altered mentalstate or diabetic ketoacidosis. The physical examinationshould include all parts of the body to search for skin inflam-mation. This is important in patients presenting with sepsiswith no obvious skin lesions. The perineum and oral cavityare areas that can be easilymissed [21]. Also a search for othersource of infection which can underlay necrotizing fascitisneeds to be made like appendicitis, perforated diverticulitis,and cholecystitis intraabdominal abscess.

Erysipelas, being an infection of the superficial dermis,haswell-defined borders and often blister. In cellulitis, there ispredominance of erythema lymphangitis with minimal blis-tering. Necrotizing fasciitis typically presents with patchy dis-colouration of the skin with pain and swelling, but without adefined margin or lymphangitis [22]. Progression of NF ismarked with the development of tense edema, a grayish-brown discharge, vesicles, bullae, necrosis, and crepitus [23](Table 5). Hemorrhagic bullae and crepitus are serious signs,with the likelihood of underlying fascia and muscle being

compromised [24]. Crepitus is a late sign and is found in onlyabout 18% of cases of NF [25]. Although crepitus and blister-ing are the most specific signs of necrotizing soft tissue infec-tion, they are not sensitive. Two retrospective case series, byWang et al. [26] and Elliott et al. [27], reported an absence ofcrepitus in 62% to 73% of cases and an absence of blistering in76% to 95% of cases upon initial presentation.There is usuallyabsence of collection of pus which delays surgical consult ordelays intervention by surgeon.

Severe localized pain is another feature of NF. As thedisease is a deep-seated infection, the epidermis is minimallyinvolved at initial presentation.Thepatientmight complain ofpain out of proportion to the degree of dermal involvementor pain that extends past the apparent margin of infection.Patients with diabetic neuropathy may have minimal painresulting in amissed diagnosis.This is especially likely in con-cealed sites of infection, such as the perineumor oral cavity. Apatch of anesthesia over the site of erythema is also sometimesdescribed in NF. This is thought to be due to infarction ofcutaneous nerves in necrotic subcutaneous fascia and softtissue [28].

There are some specific types of necrotizing fasciitis withcharacteristic features.

5.1. Necrotizing Cellulitis. Necrotizing cellulitis, or hemolyticstreptococcal gangrene, generally presents shortly afterminortrauma. Patients have findings consistent with cellulitis,including erythema, warmth, and swelling. Unlike othercellulitis severe pain is common.Theremay be rapid develop-ment of gas distal to the wound and blebs which contain darkserous fluid.

5.2. Streptococcal Myositis. The hallmarks of streptococcalmyositis are severe local pain and toxemia. Wounds have afoul odor, discoloration, and edema. Patients might developblebs and gangrene of the overlying skin, although diseaseprogression is characteristically slow. Underlying muscle isnot viable and will require excision.

5.3. Clostridial Cellulitis. One of the most important histori-cal findings associated with clostridial cellulitis is severe painoccurring days after local tissue injury. Patients subsequently


develop skin blebs that contain a reddish-brown, foul-smelling fluid. There is rapid progression of cellulitis overhours and patient is toxic. Crepitus might be noted, but it isnot a universal finding.

5.4. Progressive Bacterial Synergistic Gangrene or Meleney’sGangrene. According to Baxter, progressive bacterial syner-gistic gangrene (PBSG) and Meleney’s ulcer represent vari-ants of the same disease process, but Lewis describes them astwo separate entities. Despite differences, similar clinical pro-files are noted. PBSG is a rapidly progressive infection causedby nonhemolytic streptococci in association with hemolyticstaphylococci or gram-negative bacilli. It is most commonlyfound following abdominal surgeries with infected wound.Clinical presentation is notable for a wound with a centralnecrotic area that is surrounded by purple, erythematouszones of skin. In addition, necrotic tracts can extend throughthe underlying tissue, resulting in additional ulcerations atsites distant from the primary lesion.

5.5. Fournier’s Gangrene. Fournier’s gangrene is an acute,rapidly progressive, and potentially fatal, infective necrotiz-ing fasciitis affecting the external genitalia, perineal, or peri-anal regions, which commonly affects men but can also occurin women and children. The clinical features of Fournier’sgangrene include sudden pain in the scrotum, prostration,pallor, and pyrexia. At first only the scrotum is involved, but ifunchecked, the cellulitis spreads until the entire scrotal cover-ings slough, leaving the testes exposed but healthy. One over-whelming feature of the presentation is the strong “repulsive,fetid odour” that is associated with the condition. Patientscan present with varying signs and symptoms including fevergreater than 38∘C, scrotal swelling and erythema, purulenceor wound discharge, crepitation, or fluctulance [29].

6. Diagnostic Tools

There are a wide variety of diagnostic tools that have beendescribed and tested to diagnose NF more accurately andexpeditiously. Even in the most experienced hands, clinicalfindings are not accurate enough for diagnosis, and both clin-ical clues and diagnostic tools should be used in combinationto help make an early diagnosis.

6.1. Laboratory Testing. Abnormal laboratory findingsinclude an elevated white blood cell (WBC) count, azotemia,abnormal coagulation profiles, and decreased platelet andfibrinogen levels. Other laboratory findings such as elevatedlactate and blood glucose levels, hypocalcemia, hypoalbu-minemia, and anemia are also commonly found. The sensi-tivity of these studies varies, although leukocytosis and hyp-onatremia have been found to be predictive of necrotizinginfection.

Wall et al. [30], in a retrospective study, compared a set ofadmission variables of patients with NSTI and patients withnonnecrotizing soft-tissue infection. After univariate andmultivariate analysis, they found that having a WBC count>15,400 cells/mm3 or a serum sodium level <135mmol/L

Table 6: Laboratory risk indicator for necrotizing fasciitis(LRINEC) score to help discriminate between necrotizing andnonnecrotizing soft-tissue infections.

Value ScoreC-reactive protein, mg/dL<150 0>150 4

WBC count, cells/mm3

<15 k 015–25 k 1>25 k 2

Hemoglobin level, g/dL>13.5 011–13.5 1<11 2

Sodium level, mmol/L>135 0<135 2

Creatinine level, mg/dL<1.6 0>11.6 2

Glucose level, mg/dL<180 0>180 1

Risk category: low <5 (<50% chance of NF), intermediate 6-7 (50–75%chance of NF), and high 8 (>75% chance of NF).

was associated with NSTI and that a combination of bothincreased the likelihood of NSTI. It had a negative predictivevalue (NPV) of 99%, but not very specific, with a positivepredictive value (PPV) of only 26%.

Wong et al. [31] devised a scoring system (laboratoryrisk indicator for necrotizing fasciitis score) to discrimi-nate between NSTI and nonnecrotizing soft-tissue infec-tion (Table 6). They compared a set of laboratory variablesbetween patients with and without NSTI and identified 6independent variables associated with NSTI. The total scorehad a range of 0–13, and patients were categorized accordingto the risk of NSTI among 3 groups. Wong and colleaguesshowed that, for intermediate and high-risk patients (score>6), the score had a PPV of 92% and a NPV of 96%. Thisconstitutes a great tool for both confirming and discardingNSTI and has the advantage that it is based on laboratoryvariables that arewidely available across different institutions.

Plain X-ray films can demonstrate subcutaneous gas, butthis is a specific, not a sensitive, finding (positive in fewer than25% of cases) and absence of gas does not exclude NF [32].Computed tomography and magnetic resonance imaging(MRI) might be useful in cases where signs are equivocal ordiagnosis is in doubt. Asymmetrical fascial thickening, fatstranding, and gas tracking along fascial planes are importantimaging findings. Computed tomography scans are estimatedto have a sensitivity of 80% for detecting necrotizing soft tis-sue infections [33]. In cases of cellulitis,MRIwill demonstratesubcutaneous thickening with fluid collection. However,when there is deep fascia involvement with fluid collection,


thickening, and enhancement after contrast administration,necrotizing infections must be considered. According toSchmid et al. [34] the sensitivity of MRI is 100% with aspecificity of 86%. It is particularly helpful in the investigationof areas that have disproportionately severe tenderness andwhen nonspecific signs of sepsis are present. This has beendisputed, and other authors have argued that in early cases ofNF, MRI might not show fascial involvement [35]. If clinicalsuspicion is high, surgeons can opt to explore andperform tis-sue biopsies rather than delay treatment for imaging studies.

6.2. Biopsy. In clinically suspicious cases where there is noobvious finding tissue diagnosis may be sought. Fine needleaspiration (FNA) has been used in the past but is no longerrecommended. Incisional biopsy has largely replaced FNA asamore sensitive technique. It can be performed at the bedsideunder local anesthetic and is advocated in early or equivocalcases. Standard practice is to take biopsies from a representa-tive area of the infectious process and from the leading edgeof any erythematous, edematous, necrotic, or indurated area[36].

Frozen-section evaluation of an incisional biopsy speci-men characteristically reveals necrosis, polymorphonuclearinfiltration, microorganisms, vasculitis, and vascular throm-bosis located in the superficial fascia, deep dermis, andsurrounding adipose tissue. Sparing of epidermis, superficialdermis, and underlying muscle tissue is usually noted. Gramstain of the tissue sample is also a valuable adjunct to clinicalexamination and can be performed [37, 38].

7. Treatment

7.1. Hospitalization. Primary care physicians have to use clin-ical judgment to decide which patients who present with evi-dence of skin inflammation should be hospitalized or receivefurther evaluation. It is interesting that only 15% to 34% ofpatients with a discharge diagnosis of necrotizing skin andsubcutaneous infection had an admitting diagnosis of NF.

Studies of patients with soft tissue infection showed thata history of diabetes mellitus, pyrexia, hand infections, andan area of inflammation greater than 70 cm2 are independentpredictors of hospitalization [39]. Hospitalization is indicatedfor patients with soft tissue infections accompanied by signsand symptoms of systemic toxicity (fever, hypothermia,tachycardia (heart rate more than 100 beats/min)), hypoten-sion (systolic blood pressure less than 90mmHg or morethan 20mmHg below baseline), an altered mental state,severe infection (including those requiring formal operativeintervention), intractable nausea and vomiting, immuno-compromise, failure of outpatient therapy, and poor socialsupport. The latest Infectious Diseases Society of Americaskin and soft tissue infection guidelines indicate that hospi-talization should be considered in patients with hypotensionand/or an elevated creatinine level, low serum bicarbonatelevel, elevated creatine phosphokinase level (2-3 times theupper limit of normal), marked left shift, or a C-reactiveprotein level more than 13mg/L [40].

The treatment for NSTI involves the principles of treat-ment for any kind of surgical infection: source control, anti-microbial therapy, support, and monitoring.

7.2. General Management. Patients who have progressivenecrotizing infections oftendeteriorate rapidly. As soon as thediagnosis of NSTI is suspected, aggressive resuscitation andempiric broad-spectrum antibiotic coverage should be insti-tuted. Septic shock with intravascular volume depletion andshunting in the periphery is an ongoing process at the timeof diagnosis. Significant fluid and protein losses occur evenbefore surgical debridement, resulting in inadequate tissueoxygenation. Early resuscitation with blood products andvasopressins over crystalloids reduce mortality. Main vaso-pressins used are noradrenaline and dopamine.

Patients presenting with multiorgan failure are admittedto surgical intensive care unit (SICU). Invasive hemodynamicmonitoring is routinely implemented when the patient hasbeen admitted to the SICU with the goal being to achieve anoxygen delivery greater than 600mL/min/m2. Patients pre-senting with respiratory failure may require prolonged ven-tilation and tracheostomy is often required. Renal failure isanother frequent complication thatmight require continuoushemodialysis [41].

Aggressive nutritional support is mandatory in allpatients after debridement. Patients should receive twice theirbasal caloric requirements orally or parenterally. Nutritionalsupport is associated with fewer complications and lowermorbidity and mortality rates [42]. Pre- and postoperativepain control is also an important part of management andshould be individualized for each patient.

7.3. Antimicrobial Therapy. Antimicrobial therapy is anadjunct to source control for the treatment ofNF. Broad-spec-trum antimicrobial therapy should be started early to includecoverage for gram-positive, gram-negative, and anaerobicorganisms. Special consideration for Group A Streptococ-cus and Clostridium species should be taken. Acceptableregimens include monotherapy agents, such as imipenem,meropenem, ertapenem, piperacillin/tazobactam, and tige-cycline. Multidrug regimens have also been described,including triple-drug therapy regimens, such as high-dosepenicillin, high-dose clindamycin, and a fluoroquinolone oran aminoglycoside for coverage of gram-negative organisms.Vancomycin, daptomycin, or linezolid should be includedin the regimen until methicillin-resistant staphylococcalinfection has been excluded. The use of protein synthesisinhibitors, such as clindamycin, may help by inhibiting toxinproduction, which can be crucial for controlling the inflam-matory response in patients with NSTI, particularly in thosewith clostridial and streptococcal infections. Antimicrobialadministration should be continued until no further debride-ments are needed and the patient’s physiology has improved.Prolonged courses of an arbitrary duration are not necessaryand may predispose the patient to wound colonization withdrug-resistant organisms.

In type 2 NF caused by streptococci resulting in strepto-coccal toxic shock syndrome, intravenous immunoglobulins


might play a therapeutic role. A multicentre, randomizedcontrolled trial evaluated the safety and efficacy of intra-venous immunoglobulins in streptococcal toxic shock syn-drome. The trial was prematurely stopped because of poorrecruitment, but it showed 3.6-fold higher mortality in theplacebo group compared with the treatment group [43].These studies are also controversial and difficult to compare,given the small number of patients and the different method-ologies used. It seems reasonable to use intravenous immuneglobulin in patients with groupA streptococcal infectionwhohave developed streptococcal toxic shock syndrome and inthose with a high mortality risk (advanced age, hypotension,and bacteremia) [44].

7.4. SurgicalManagement. WheneverNFhas been confirmedsurgical debridement is indicated. Some researchers alsoadvocate surgery as a means for diagnosis in patients forwhom clinical and laboratory findings are still not conclusiveand for whom the diagnosis of NF is still possible. Debride-ment of the necrotic tissue should be undertaken as soon aspossible. Other researchers have clearly shown the impact ofearly and complete debridement on final outcome in patientswith NF [45, 46].

When comparing earlier and complete with delayed orincomplete debridements, mortality always has been signif-icantly lower with the most aggressive strategy. Importantgoals of debridement include removal of heavily contami-nated tissue and removal of all devitalized tissues that mightotherwise impair host defenses within the wound. Persistentnecrotic tissue serves as a culture medium and creates ananaerobic environment in which the bactericidal activity ofpolymorphonuclear cells is impaired. During the operation,a generous incision is performed andmacroscopic findings ofthe disease are used to help guide the extent of the debride-ment. An indication of muscle viability is by its responseto stimulation using hand-held cautery. When contractilityis absent, the muscle is usually not viable and should bedebrided.

Intraoperative administration of intravenous fluoresceincan be used to determine viability of adjacent soft tissueswhen viewed under a Wood’s or ultraviolet (UV) lamp. Tenminutes after injection of one ampule of fluorescein, exposureof the operative field to UV light will expose nonperfusedareas that require further debridement. Occasionally, ampu-tation of a limb is necessary to achieve this goal and is encour-aged if that is the case. Healthy, viable, bleeding tissue shouldbe present at the edges of the excision site, and aggressiveresuscitation should accompany the perioperative period.Once the initial debridement has been done, managementin an intensive care unit is recommended, and scheduleddebridements at intervals of 6–48 h should be performeduntil no further necrosis or infected tissue is seen.

7.5. Hyperbaric Oxygen Therapy. Hyperbaric oxygen (HBO)is generally considered to be an important adjunct in thetreatment of clostridial myonecrosis or gas gangrene. Allnecrotizing infections are associated with reduced tissueoxygen tension, ischemia, and subsequent decrease in host

cellular immunity. Increased oxygen partial pressure has beenassociated with the reversal of basic pathophysiologic mech-anisms of necrosis. Increased oxygen tension also reversesischemia and thereby improves host defense mechanisms[47, 48]. HBO also enhances the action of various antibioticagents by facilitating their transport across the bacterial cellwall. Various studies have failed to show statistically signifi-cant outcome differences with respect tomortality and lengthof hospitalization [49]. As a result, HBO is not a mandatorycomponent of therapy. It might be appropriate in somepatients, but its use should never delay definitive surgical care.An HBO treatment regimen usually consists of wound expo-sure at 2.5 to 3.0 atmospheres and breathing 100% oxygen for90minutes every 8 hours for the first 24 hours and then twicedaily. HBO treatment is continued for a minimum of 5 daysand is discontinued when the patient is stable and has noevidence of ongoing necrosis [50].

8. Prognosis

Since the first description by Jones, mortality in patients withNSTI remains high. He reported a mortality rate of 46%, anda recent pooled analysis determined it to be ∼34% [51].

More recent data indicate a mortality of 16.4% [52] forcommunity-acquired necrotizing soft tissue infections and36.3% for postprocedural necrotizing infections [53]. All ofthese patients were managed in hospital with intravenousantibiotics and surgical interventions; considering medicalprogress in the last 135 years, mortality is still substantial.Mortality is higher in patients with streptococcal toxic shocksyndrome. Diabetic patients, especially those presenting withdiabetic ketoacidosis or hyperosmolar hyperglycemic nonke-totic acidosis, have higher rates of death and longer lengths ofhospital stay [54]. A delay in surgery of more than 24 hourswas an independent risk factor for mortality.

In a recent study that included 350 patients with NF,Anaya et al. [55] created a score to categorize patients accord-ing to the risk of mortality. Variables included in the scorewere age >50 years, WBC count >40,000 cells/mm3, hema-tocrit >50%, heart rate >110 beats/min, temperature >36degrees Celsius, and creatinine level >1.5mg/dL. Tools likethis should help to identify high-risk patients whomay bene-fit fromnovel therapeutic strategies or for selection of patientsfor future trials.

There is also considerable postoperativemorbidity, some-times from extensive debridement resulting in muscle loss.Patients might have to undergo a period of rehabilitation toregain function of the affected areas. Scarring and disfigure-ment can also be substantial.

9. Summary

NSTIs are relatively infrequent but highly lethal infections.They encompass a wide variety of soft-tissue infectionsassociated with necrosis that share the same diagnostic andtreatment principles. Establishing the diagnosis of NSTI isone of the biggest challenges in treating patients with NSTI.Accuracy increases with familiarity of clinical findings and


knowledge of laboratory, imaging, and macroscopic andmicroscopic findings, all combined with a high index of sus-picion. Treatment includes definitive surgical debridement inconjunctionwith antimicrobials and hemodynamic stabiliza-tion. Surgical debridement should be performed frequently(even daily) until the acute tissue destruction has been con-trolled. Outcomes are also influenced by prompt diagnosis,the timing and extent of surgical treatment, andmanagementof postoperative complications. Scores that identify high-riskpatients serve to guide novel therapeutic strategies and toidentify patients for future trials.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

References

[1] J. Jones, “Surgicalmemoirs of the war of the rebellion: investiga-tion upon the nature, causes and treatment of hospital gangreneas prevailed in the Confederate armies 1861–1865,” US SanitaryCommission, New York, NY, USA, 1871.

[2] N. Eke, “Fournier’s gangrene: a review of 1726 cases,” BritishJournal of Surgery, vol. 87, no. 6, pp. 718–728, 2000.

[3] F. Meleney, “Hemolytic streptococcus gangrene,” Archives ofSurgery, vol. 9, pp. 317–364, 1924.

[4] B.Wilson, “Necrotizing fasciitis,”TheAmerican Surgeon, vol. 18,no. 4, pp. 416–431, 1952.

[5] A. F. Hefny, H. O. Eid, M. Al-Hussona, K. M. Idris, and F.M. Abu-Zidan, “Necrotizing fasciitis: a challenging diagnosis,”European Journal of Emergency Medicine, vol. 14, no. 1, pp. 50–52, 2007.

[6] C.-H. Wong, H.-C. Chang, S. Pasupathy, L.-W. Khin, J.-L.Tan, and C.-O. Low, “Necrotizing fasciitis: clinical presentation,microbiology, and determinants of mortality,” Journal of Boneand Joint Surgery A, vol. 85, no. 8, pp. 1454–1460, 2003.

[7] C. R. Baxter, “Surgical management of soft tissue infections,”Surgical Clinics of North America, vol. 52, no. 6, pp. 1483–1499,1972.

[8] R. Lewis, “Necrotizing soft tissue infections,” in Surgical Infec-tions in Critical Care Medicine, J. L. Meakins, Ed., pp. 153–171,Churchill Livingstone, London, UK, 20th edition, 1985.

[9] N. Forbes and A. P. Nigel Rankin, “Necrotizing fasciitis and nonsteroidal anti-inflammatory drugs: a case series and review ofthe literature,” New Zealand Medical Journal, vol. 114, no. 1124,pp. 3–6, 2001.

[10] W. Tung-Yiu, H. Jehn-Shyun, C. Ching-Hung, andC.Hung-An,“Cervical necrotizing fasciitis of odontogenic origin: a report of11 cases,” Journal of Oral and Maxillofacial Surgery, vol. 58, no.12, pp. 1347–1352, 2000.

[11] P. Clark, D. Davidson, M. Letts, L. Lawton, and A. Jawadi,“Necrotizing fasciitis secondary to chickenpox infection inchildren,” Canadian Journal of Surgery, vol. 46, no. 1, pp. 9–14,2003.

[12] S. Frick and A. Cerny, “Necrotizing fasciitis due to Streptococcuspneumoniae after intramuscular injection of nonsteroidal anti-inflammatory drugs: report of 2 cases and review,” ClinicalInfectious Diseases, vol. 33, no. 5, pp. 740–744, 2001.

[13] L. G. Svensson, A. J. Brookstone, andM.Wellsted, “Necrotizingfasciitis in contused areas,” Journal of Trauma, vol. 25, no. 3, pp.260–262, 1985.

[14] B. J. Childers, L. D. Potyondy, R. Nachreiner et al., “Necrotizingfasciitis: a fourteen-year retrospective study of 163 consecutivepatients,” American Surgeon, vol. 68, no. 2, pp. 109–116, 2002.

[15] D. L. Stevens, “Could nonsteroidal antiinflammatory drugs(NSAIDs) enhance the progression of bacterial infections totoxic shock syndrome?” Clinical Infectious Diseases, vol. 21, no.4, pp. 977–980, 1995.

[16] D. M. Aronoff and K. C. Bloch, “Assessing the relationshipbetween the use of nonsteroidal antiinflammatory drugs andnecrotizing fasciitis caused by group A streptococcus,” Medi-cine, vol. 82, no. 4, pp. 225–235, 2003.

[17] C.-T. Hsiao, H.-H. Weng, Y.-D. Yuan, C.-T. Chen, and I.-C.Chen, “Predictors of mortality in patients with necrotizingfasciitis,” American Journal of Emergency Medicine, vol. 26, no.2, pp. 170–175, 2008.

[18] D. Elliott, J. A. Kufera, andR.A.M.Myers, “Themicrobiology ofnecrotizing soft tissue infections,” American Journal of Surgery,vol. 179, no. 5, pp. 361–366, 2000.

[19] E. K. Chapnick and E. I. Abter, “Necrotizing soft-tissue infec-tions,” Infectious Disease Clinics of North America, vol. 10, no. 4,pp. 835–855, 1996.

[20] T. L. Bosshardt, V. J. Henderson, and C. H. Organ Jr., “Necrotiz-ing soft-tissue infections,”Archives of Surgery, vol. 131, no. 8, pp.846–854, 1996.

[21] M. K. Hill and C. V. Sanders, “Necrotizing and gangrenous softtissue infections,” in The Skin and Infection: A Color Atlas andText, C. V. Sanders and L. T.Nesbitt Jr, Eds., pp. 62–75, Lipincott,Williams &Wilkins, Baltimore, Md, USA, 1995.

[22] R. J. Green, D. C. Dafoe, and T. A. Raffin, “Necrotizing fasciitis,”Chest, vol. 110, no. 1, pp. 219–229, 1996.

[23] A. J. Headley, “Necrotizing soft tissue infections: a primary carereview,” American Family Physician, vol. 68, no. 2, pp. 323–328,2003.

[24] C.-T. Hsiao, L.-J. Lin, C.-J. Shiao, K.-Y. Hsiao, and I.-C. Chen,“Hemorrhagic bullae are not only skin deep,” American Journalof Emergency Medicine, vol. 26, no. 3, pp. 316–319, 2008.

[25] L. A. Sudarsky, J. C. Laschinger, G. F. Coppa, and F. C. Spencer,“Improved results from a standardized approach in treatingpatients with necrotizing fasciitis,” Annals of Surgery, vol. 206,no. 5, pp. 661–665, 1987.

[26] Y.-S. Wang, C.-H. Wong, and Y.-K. Tay, “Staging of necrotizingfasciitis based on the evolving cutaneous features,” InternationalJournal of Dermatology, vol. 46, no. 10, pp. 1036–1041, 2007.

[27] D. C. Elliott, J. A. Kufera, and R. A. M. Myers, “Necrotizingsoft tissue infections: risk factors for mortality and strategies formanagement,” Annals of Surgery, vol. 224, no. 5, pp. 672–683,1996.

[28] S. Dufel and M. Martino, “Simple cellulitis or a more seriousinfection?” Journal of Family Practice, vol. 55, no. 5, pp. 396–400,2006.

[29] M. N. Mallikarjuna, A. Vijayakumar, V. S. Patil, and B. S. Shiv-swamy, “Fournier’s gangrene: current practices,” ISRN Surgery,vol. 2012, Article ID 942437, 8 pages, 2012.

[30] D. B. Wall, S. R. Klein, S. Black, and C. De Virgilio, “A simplemodel to help distinguish necrotizing fasciitis from nonnecro-tizing soft tissue infection,” Journal of the American College ofSurgeons, vol. 191, no. 3, pp. 227–231, 2000.


[31] C.-H. Wong, L.-W. Khin, K.-S. Heng, K.-C. Tan, and C.-O.Low, “The Laboratory Risk Indicator for Necrotizing Fasciitis(LRINEC) score: a tool for distinguishing necrotizing fasciitisfrom other soft tissue infections,” Critical Care Medicine, vol.32, no. 7, pp. 1535–1541, 2004.

[32] Y.-J. Lim, F.-C. Yong, C.-H. Wong, and A. B. H. Tan, “Necro-tising fasciitis and traditional medical therapy—a dangerousliaison,” Annals of the Academy of Medicine Singapore, vol. 35,no. 4, pp. 270–273, 2006.

[33] M. G. Wysoki, T. A. Santora, R. M. Shah, and A. C. Friedman,“Necrotizing fasciitis: CT characteristics,” Radiology, vol. 203,no. 3, pp. 859–863, 1997.

[34] M. R. Schmid, T. Kossmann, and S. Duewell, “Differentiation ofnecrotizing fasciitis and cellulitis usingMR imaging,”AmericanJournal of Roentgenology, vol. 170, no. 3, pp. 615–620, 1998.

[35] A. Arslan, C. Pierre-Jerome, and A. Borthne, “Necrotizingfasciitis: unreliable MRI findings in the preoperative diagnosis,”European Journal of Radiology, vol. 36, no. 3, pp. 139–143, 2000.

[36] J. Fildes, M. P. Bannon, and J. Barrett, “Soft-tissue infectionsafter trauma,” Surgical Clinics of NorthAmerica, vol. 71, no. 2, pp.371–384, 1991.

[37] I. Stamenkovic and P. D. Lew, “Early recognition of potentiallyfatal necrotizing fasciitis.The use of frozen-section biopsy,”NewEngland Journal of Medicine, vol. 310, no. 26, pp. 1689–1693,1984.

[38] J. Majeski and E. Majeski, “Necrotizing fasciitis: improvedsurvival with early recognition by tissue biopsy and aggressivesurgical treatment,” SouthernMedical Journal, vol. 90, no. 11, pp.1065–1068, 1997.

[39] D. B. Diercks, N. Kuppermann, R. W. Derlet, and A. A. Ernst,“Derivation and validation of a model for the need of hospitaladmission in patients with extremity cellulitis,”Academic Emer-gency Medicine, vol. 7, no. 5, p. 562, 2000.

[40] D. L. Stevens, A. L. Bisno, H. F. Chambers et al., “Practiceguidelines for the diagnosis and management of skin and soft-tissue infections,” Clinical Infectious Diseases, vol. 41, no. 10, pp.1373–1406, 2005.

[41] J. D. Cunningham, L. Silver, andD. Rudikoff, “Necrotizing fasci-itis: a plea for early diagnosis and treatment,”Mount Sinai Jour-nal of Medicine, vol. 68, no. 4-5, pp. 253–261, 2001.

[42] J. A. Majeski and J. W. Alexander, “Early diagnosis, nutritionalsupport, and immediate exensive debridement improvesurvivalin necrotizing fasciitis,” American Journal of Surgery, vol. 145,no. 6, pp. 784–787, 1983.

[43] J. Darenberg, N. Ihendyane, J. Sjolin et al., “Intravenous immu-noglobulin G therapy in streptococcal toxic shock syndrome: aEuropean randomized, double-blind, placebo-controlled trial,”Clinical Infectious Diseases, vol. 37, no. 3, pp. 333–340, 2003.

[44] R. Kaul, A. McGeer, D. E. Low et al., “Population-based surveil-lance for group A streptococcal necrotiziug fasciitis: clinicalfeatures, prognostic indicators, and microbiologic analysis ofseventy-seven cases,”American Journal ofMedicine, vol. 103, no.1, pp. 18–24, 1997.

[45] B. D. Bilton, G. B. Zibari, R. W. McMillan, D. F. Aultman, G.Dunn, and J. C.McDonald, “Aggressive surgicalmanagement ofnecrotizing fasciitis serves to decreasemortality: a retrospectivestudy,” American Surgeon, vol. 64, no. 5, pp. 397–401, 1998.

[46] S. T. Lille, T. T. Sato, L. H. Engrav, H. Foy, and G. J. Jurkovich,“Necrotizing soft tissue infections: obstacles in diagnosis,” Jour-nal of the American College of Surgeons, vol. 182, no. 1, pp. 7–11,1996.

[47] J. A. Riseman, W. A. Zamboni, A. Curtis, D. R. Graham, H. R.Konrad, andD. S. Ross, “Hyperbaric oxygen therapy for necrot-izing fasciitis reducesmortality and the need for debridements,”Surgery, vol. 108, no. 5, pp. 847–850, 1990.

[48] A. Shupak, O. Shoshani, I. Goldenberg, A. Barzilai, R.Moskuna,and S. Bursztein, “Necrotizing fasciitis: an indication for hyper-baric oxygenation therapy?” Surgery, vol. 118, no. 5, pp. 873–878,1995.

[49] D. R. Brown, N. L. Davis, M. Lepawsky, J. Cunningham, and J.Kortbeek, “Amulticenter review of the treatment of major trun-cal necrotizing infections with and without hyperbaric oxygentherapy,” American Journal of Surgery, vol. 167, no. 5, pp. 485–489, 1994.

[50] M. Harris and D. Young, “Hyperbaric medicine. A specializedmode of treatment that is gaining acceptance,” Indiana Medi-cine, vol. 80, no. 3, pp. 258–261, 1987.

[51] C. R.McHenry, J. J. Piotrowski, D. Petrinic et al., “Determinantsof mortality for necrotizing soft-tissue infections,” Annals ofSurgery, vol. 221, no. 5, pp. 558–565, 1995.

[52] B.W. Frazee, C. Fee, J. Lynn et al., “Community-acquired necro-tizing soft tissue infections: a review of 122 cases presenting to asingle emergency department over 12 years,” Journal of Emer-gency Medicine, vol. 34, no. 2, pp. 139–146, 2008.

[53] A. T. Miller, P. Saadai, A. Greenstein, and C. M. Divino,“Postprocedural necrotizing fasciitis: a 10-year retrospectivereview,” American Surgeon, vol. 74, no. 5, pp. 405–409, 2008.

[54] O. Oncul, C. Erenoglu, C. Top et al., “Necrotizing fasciitis: alife-threatening clinical disorder in uncontrolled type 2 diabeticpatients,” Diabetes Research and Clinical Practice, vol. 80, no. 2,pp. 218–223, 2008.

[55] D. A. Anaya, K.McMahon, A. B. Nathens, S. R. Sullivan, H. Foy,and E. Bulger, “Predictors ofmortality and limb loss in necrotiz-ing soft tissue infections,”Archives of Surgery, vol. 140, no. 2, pp.151–157, 2005.

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