Necrotizing Soft Tissue Infection

Necrotizing Soft Tissue Infection

Abstract

A 49 year old gentleman was diagnosed with necrotising fasciitis of right leg. He underwent an above knee amputation of right leg due to fast spreading infection. His recovery was complicated by hospital acquired pneumonia.

Keywords: necrotizing fasciitis, soft tissue infections, cellulitis.

Introduction

Necrotizing soft tissue infections (NSTIs) constitute a spectrum of disease processes characterized by fulminant, widespread necrosis of soft tissue, systemic toxicity, and high mortality. It can be classified based on a variety of criteria including etiologic, microbiologic, anatomic, and clinical aspects. Clinically it is classified as superficial or deep infection. Superficial infections (necrotizing cellulitis) are those confined to the cutis and subcutis, such as erysipelas. Deep infection is the infection affecting fascia and muscle, including necrotizing fasciitis and myonecrosis.

Case Report (M766197)

A case of a 49 year old malay gentleman presented to emergency department PPUKM with pain and swelling of his right leg since past one week. He had high grade fever prior to the development of swollen leg and continued to have fever during admission. He is a known diabetic patient on follow-up with PPUKM. On examination, he was ill-looking with high grade fever, tachycardic and dehydrated. The ulcer on his right foot was foul smelling and the swelling had gone up to the knee. Crepitus was felt on the right calf. Plain radiographs of the right leg showed subcutaneous gas shadow extending up to the right knee. The blood parameters showed raised CRP and ESR (29.19 mg/dl and 99mm/hr respectively), raised total white blood cells (13.7 x 10⁹/L) but normal renal and liver profile.

After discussion with the patient regarding his condition and treatment options, he agreed for the operation. He was planned for a below knee kiv above knee amputation. We proceeded with above knee amputation as the infection had reached the proximal tibia. Intraoperative findings during wound exploration include seropurulent discharge drained from the space beneath the deep fascia and gaseous substance released as the skin breached. The deep fascia was also easily detached and separated from the deep and superficial layer. The wound at the amputation site was fairly healthy. The operation was uneventful.

He developed hospital acquired pneumonia postoperatively and was managed accordingly by the respiratory team.

Discussion

Introduction

Necrotizing soft-tissue infections (NSTIs) are often dramatic and life-threatening illnesses. It has been recognized since the fifth century where it was first described by Hippocrates.¹ Various names has been given to this disease such as gangrenous ulcer, hospital gangrene, Meleney gangrene² and Fournier gangrene³. In the 1990’s it became popularly known in media as the “flesh-eating bacteria” disease.⁴ The mortality rate associated with this condition ranges from 9% to 29%.^5,6,7 There are approximately 500–1500 cases of NSTIs per year in the US with the mortality rate is approximately 24–34%.⁸

Aetiology

There are many factors involve in the aetiology of necrotizing soft tissue infections. It can be as trivial as insect bites to suppurative surgical infections. It can occur in any part of the body but more commonly seen in the abdominal wall, perineum and both upper and lower limbs. The organism usually enters via either direct inoculation or hematogenous spread. In some cases, however, no primary cause can be found. Patients often have some prior history of trauma (which may even be trivial), such as an insect bite, scratch, or abrasion.⁹ Most patients who develops NSTI have a premorbid condition such as diabetic mellitus, chronic diseases, overzealous steroids user, malnutrition, intravenous drug abuser, peripheral vascular disease, renal failure, malignancy and obesity.

Clinical presentation

Patients usually presents with signs of inflammation such as erythema, swelling and pain (stage 1) (Table 1). It is difficult to differentiate between NSTI and cellulitis in the early stage of the disease. The key factor is pain disproportionate to the amount of “redness.” If a cellulitis fails to respond to antibiotics within 24–48 hr, NSTI must be considered.¹⁰

Table 1: Clinical features of necrotizing fasciitis as the disease progress through clinical stages. (Wong: Curr Opin Infect Dis, Volume 18(2).April 2005.101–106)

As the disease progress, frequently very rapidly, there is significant pain at wound site, accompanied by increasing erythema, edema, and warmth. The surrounding skin tissue may further deteriorate and become discolored. Blister or bulla formation is an important diagnostic clue.⁵ When present, it signals the onset of critical skin ischemia (stage 2). Blisters are caused by ischemia-induced necrolysis as the vessels coursing through the fascia to supply the skin are progressively thrombosed by the invading organisms. Lymphangitis is rarely seen NSTI. The late stage (stage 3 necrotizing fasciitis) signals the onset of tissue necrosis and is characterized by the so call ‘hard signs’ of necrotizing soft tissue infection such as hemorrhagic bullae, skin anesthesia and frank skin gangrene. Within 4–5 days of the appearance of the first symptoms, patients may demonstrate critical symptoms, including numbness, hypotension, toxic shock, and unconsciousness. The disease may progress to gangrene, sepsis, and potential death.¹¹

Microbiology

A single species of bacteria itself, or a polymicrobial infection may be responsible for NSTI.¹⁸ There are three clinical subtypes exist. Type I is polymicrobial. It is a mixed infection caused by aerobic and anaerobic bacteria, and occurs most commonly after surgical procedures and in patients with diabetes and peripheral vascular disease. Type II is monomicrobial. This condition can be associated with Toxic Shock Syndrome and tends to occur in healthy, young and immunocompetent individuals. The culprit microbe is typically Streptococcus (group A [beta] haemolytic streptococci).⁷ The least common subtype is type III. It is caused by Vibrio vulnificus. This condition is seen in skin break due to exposure to warm sea water and also in severe liver disease eg chronic hepatitis B. Group A streptococci are typically considered as extracellular pathogens but have been shown to survive intracellularly in macrophages during acute invasive infections.¹² This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication. Streptococcus group G is rarely implicated in NSTI but its associated mortality could be comparable to that induced by S. pyogenes.¹³ Staphylococcus aureus and other staphylococci are also known causes of NSTIs.¹⁴

Pathophysiology

Necrotizing infection develops as pathogens proliferate within subcutaneous tissue along superficial and deep fascial planes. Surface proteins, enzymes and toxins released by the pathogens play an important role in NSTI. Surface proteins M-1 and M-3 increase the adhesion of streptococci to tissues and prevent phagocytosis by neutrophils.¹⁵ Streptococcal pyrogenic exotoxins A, B, and C and streptococcal superantigen cause the release of cytokines such as TNF α, IL-1, and IL-6, and set in motion of a destructive process that may lead to toxic shock syndrome.¹⁶ Necrosis of superficial fascia and fat produces watery, thin and foul-smelling fluid described as ‘dishwater pus’. The precise mechanism of liquefactive necrosis is not clear. Possibly from bacterial enzymes like hyaluronidase and lipase which degrades the fascia and fat.

Skin involvement can develop in time due to thrombosis of the perforating vessels to the skin. Thrombosis of skin perforating vessels is caused by local hypercoagulable state, platelet-neutrophil plug which block the vessels. As infection progresses and greater quantities of toxins are produced and absorbed, local ischemia likely expands regionally until an entire tissue bed is destroyed. Systemically, microvascular occlusion may also contribute to the shock and organ dysfunction associated with these infections.

Diagnosis

Establishing diagnosis is very important. A delay in diagnosis leads to delayed surgical debridement, which leads to higher mortality.¹⁷ The diagnosis relies on high clinical index of suspicion. History taking and physical examination plays an important role in diagnosing this condition. The classic presentation of myonecrosis is that of severe pain and underlying crepitus. The patient generally appears ill and has a rapid pulse and significant temperature elevation. Numbness is a unique finding in NSTI. Skin anesthesia probably is due to infarction of the cutaneous nerves located in necrotic subcutaneous fascia and soft tissue. The findings of crepitus on palpation and soft tissue air on plain radiography are pathognomonic, although these signs are present in only 37% and 57% of the cases, respectively.¹⁸ As the infection spreads along the fascial planes, painless, black, necrotic plaque-like ulcers may appear.

The use of ultrasonography, computed tomography, and MRI can be helpful for patients with other sources of infection, particularly deep abscesses. Computed tomography is better in showing abnormal soft tissue gas compared to plain radiograph.¹⁹ CT scan may also show fascial thickening, fascial stranding, and asymmetric thickening of fascial planes. Magnetic resonance imaging (MRI) with gadolinium contrast enhancement can accurately determine the presence of necrosis of fascia and the extent of the infectious and necrotic process.²⁰ The sensitivity of MRI, however, exceeds its specificity.²¹ A bedside frozen tissue section biopsy is an expedient method by which to establish the diagnosis on the basis of typical histologic changes of subcutaneous necrosis, polymorphonuclear cell infiltration, fibrinous vascular thrombosis with necrosis, microorganisms within the destroyed fascia and dermis, and sparing of muscle.^22,23

Laboratory Risk Indicator For Necrotising Fasciitis’ developed by Wong et al¹³ gives the guideline to diagnose necrotizing fasciitis.²⁴ Score 6 or more has Positive Predictive Value of 96% and Negative Predictive Value of 4%. If the score is >7, the probability of necrotizing fasciitis is >75%.

Variables	Score
C-reactive protein
<150	0
≥150	4
WBC (cells/mm3)
<15	0
15-25	1
>25	2
Hemoglobin (g/dL)
>13.5	0
11-13.5	1
<11	2
Sodium (mmol/L)
≥135	0
<135	2
Creatinine (mcg/L)
≤141	0
>141	2
Glucose (mmol/L)
≤10	0
>10	1

A sum ≥6 has a high correlation with soft tissue infections.

Table 2: Variables in laboratory diagnosis of necrotizing fasciitis.

The most crucial element in the evaluation is examination by a surgeon, including surgical exploration of suspected NSTI to confirm or refute the diagnosis.¹⁴ Intra-operative findings include ‘dishwater’ discharge, tissue necrosis, lack of bleeding from dissected tissues and loss of normal resistance of fascia during finger dissection.

Treatment

Treatment of the patient usually is best managed by a team comprising the infectious disease and critical care specialists and the surgeon. Physiologic support, combined with close monitoring in an intensive care unit setting, is crucial. Given the prolonged need for complex multidisciplinary care these patients require, patients with NSTI’s may be best managed at specialized wound management facilities such as burn centers.²⁵

Broad-spectrum antimicrobial therapy should be administered empirically as soon as possible, and should cover Gram-positive, Gram-negative, and anaerobic organisms.¹⁸ Monotherapy or multidrug regimens may be used in the treatment. Imipenem by virtue of their high [beta]-lactamase resistance, wide-spectrum efficacy, and inhibition of endotoxin release from aerobic (ie, Gram-negative) bacilli, may be the initial agents of choice for treatment of the frequent polymicrobial infections that result in necrosis or skin and soft tissue.²⁶ Addition of vancomycin, linezolid or daptomycin to a carbapenem or [beta]-lactam/[beta]-lactamase inhibitor combination if methicillin-resistant S. aureus is suspected.²⁷ A regimen that includes high-dose penicillin, high-dose clindamycin, and a fluoroquinolone or aminoglycoside may be used to cover Gram-negative organisms. Clindamycin covers anaerobes well and inhibits M protein and exotoxin secretion by group A Streptococcus sp., which may be crucial for controlling the inflammatory response. Ampicillin and gentamicin represent alternatives for coverage of aerobic Gram-negative bacilli,²⁸ but an aminoglycoside must be used with extreme caution in patients with hypovolemia, shock, or preexisting renal dysfunction. Metronidazole may be employed for antianaerobic coverage. Ampicillin-sulbactam lacks adequate coverage of Pseudomonas spp. and Enterobacteriaceae.²⁹ Newer antibacterial agents, such as linezolid and quinupristin/dalfopristin, are increasingly being studied in children for the treatment of skin and soft tissue infections.³⁰ Antimicrobial administration should be continued until no further debridements are needed and the patient's physiology has improved,³¹ but no specific guidelines exist as to duration of therapy. The antibiotic regimen should be reassessed based on culture and sensitivity results. Prolonged courses of an arbitrary duration are not necessary and may predispose the patient to wound colonization with drug-resistant organisms.³²

Destruction of the local microcirculation impairs the delivery of antibiotics to the site of infections. Because of the lack of antibiotic penetration, surgical debridement is the only effective treatment for the subcutaneous ‘sequestrum’. The most important determinant of mortality is timing & adequacy of debridement.³³ Mortality increases by 9 fold if surgery is delayed by more than 24 hrs.⁵ As patient who is diagnosed with necrotizing fasciitis usually came to the hospital in unstable condition, the goal is to perform definitive surgery regardless of how radical at the first occasion. A thorough and adequate debridement is a must as patient condition will deteriorate and might not survive a second look debridement. Wound reevaluation must be performed in 24-48 hours. Second debridement may be necessary to control the infection. In the event of fast spreading infection despite aggressive debridement or necrosis involving most muscle group of the limb which leads to a useless limb, an amputation may be necessary.

Wong et al³⁴ introduced radical excisional debridement. He classified skin and subcutaneous component into 3 surgical zones (figure 1).

Figure 1: Zone 1: Non viable, gangrene, fixed discoloration, haemorrhagic bullae. b) Zone 2: Early NF skin changes, ‘woody hard’ skin texture. Potentially salvageable, must be assessed carefully. Zone 3: Healthy, normal skin

Post excision wound care is important as large raw wound is at risk of post op bleeding and also risk of secondary infection. Initially, the wound can be covered with non-adherent dressing such as soffratulle dressing followed by firmly applied pressure dressing. The wound assessment should include observation for expansion of erythema or an increase in edema, pain, color, or drainage. Advances in wound management have led to negative pressure wound therapy as a treatment for managing the closure of wounds.³⁵ Negative pressure wound therapy promotes wound healing by enhancing blood flow to and from the wound bed, increasing the proliferation of granulation tissue, and decreasing the tissue bacterial counts. Wound vacuum-assisted devices also help relieve pain at the site by removing irritating exudates that cause pressure on the wound.

Hyperbaric oxygen therapy therapy (HBOT) has been proposed for improving the outcome of NST.^18,36 In HBOT, patient were subjected to 100% oxygen at 2-3 times the atmospheric pressure with arterial oxygen tension as high as 2000 mmHg. This will inhibit anaerobes and clostridium sp. exotoxin, enhances killing ability of leukocytes and enhances efficacy of intravenous antibiotics by increase local oxygen tension in tissue.³⁷

Intravenous immunoglobulin (IVIG) may be a useful adjunct treatment in type II group A streptococcal NSTI complicated by toxic shock syndrome, and in those with a high mortality risk (advanced age, hypotension, and bacteremia). The action of IVIG is believed to be the neutralization of superantigen activity and reduced plasma concentrations of TNF[alpha] and IL-6.³⁶

Nutritional support for the patient with NSTI helps heal these extensive wounds. The amount of calories and proteins should be double that of the normal basal requirement.³⁸ To ensure that the patient is receiving adequate nutrition, baseline and repeated monitoring of albumin, prealbumin, transferrin, BUN, and triglycerides should be performed. These patients may also require supplements including iron, vitamin C, and vitamin E to promote wound healing.

Physical therapy is an important part of the plan of care for the patient with NSTI. Encouraging mobility, increasing range of motion of extremities, and participating in activities of daily living (ADLs) will promote circulation and tissue perfusion. These activities can prevent complications associated with immobility such as deep vein thrombosis and pneumonia.

There can be psychological consequences of NSTI resulting from intense discomfort, serial surgical debridements, painful dressing changes, physical disfigurement, and a myriad of emotions such as anxiety, worry, guilt, anger, and hopelessness. An ongoing psychological and psychosocial supports are needed in these patients. Supportive counselors can help patients cope with pain, anxiety, and body image disturbances caused by the appearance of extensive reconstructive surgery and interventions. Antidepressant medications may reduce feelings of depression and hopelessness.

Conclusion

Althought NSTIs are rare, they are life-threatening processes. The very young and very old are at especially high risk of an adverse outcome. The key to overcoming the risk of this disease process is in rapid identification and prompt treatment. Gold standard diagnostic tool and treatment is still thorough wound debridement and exploration. Postoperative wound care and psychological supports are important in managing NSTI.

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