Title : Necrotizing Soft Tissue Infections - A Review

Running title : Necrotizing Soft Tissue Infections

Authors : 1.Maj. Amit Kumar Shah, MBBS, MS, DNB (Gen Surg),*

Assistant Professor

Department of Surgery,

Armed Forces Medical College,

Pune, Maharashtra, India - 411040

Tele: 91-20-26306016

Fax: 91-20-26363301

Mobile no: 91-9373308006

amit_akshatshah@yahoo.co.in

2. Col. Rajan Chaudhry, MBBS, MS, DNB

Professor & Head of Department,

Department of Surgery,

Armed Forces Medical College,

Pune, Maharashtra, India - 411040

rajan5855@rediffmwil.com

* Corresponding Author

Word count : Abstract: 321 Article: 2225

NECROTIZING SOFT TISSUE INFECTIONS – A REVIEW

ABSTRACT

Necrotizing soft tissue infections (NSTI) are relatively common infections that often

present for medical attention late in their course. The diagnosis is often missed at initial

presentation, allowing further progression of the infectious process. Initially, NSTI is

manifested by severe pain localized at the trauma site. However, this is disproportionate

to the physical findings, as skin usually doesn’t carry any infection signs. Systematic

clinical symptoms, such as hypotension, fever (temperature > 38°C), tachycardia,

tachypnoea, mental disturbance, tremor, and laboratory findings of marked increase in

white blood cell count and metabolic acidosis are advanced indices of development of

sepsis. Predisposing factors of NSTI include advanced age, diabetes mellitus,

malnutrition or obesity, chronic alcoholism, drug abuse, corticosteroid use etc.

Pathogenesis of severe NSTI is known to be multibacterial. Infections, especially, in the

abdominal wall and perianal area are multibacterial with both aerobic and anaerobic

Gram-positive and negative organisms. However, infections in limbs are usually due to a

single microorganism arising from the skin flora such as Staphylococcus pyogenes. Once

the diagnosis of NSTI is made, treatment should be instituted promptly. Resuscitation,

based on the clinical state of the patient, includes aggressive fluid replacement to manage

acute renal failure from ongoing sepsis and shock. Intravenous antibiotics are given and

appropriate measures are taken to maintain cardiac output and pulmonary stability. Urine

output should be monitored via an indwelling urinary catheter. Quick and aggressive

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surgical treatment improves survival compared to delayed surgical intervention. The

degree of body area involvement, incomplete surgical debridement, WBC >15400/cmm,

serum sodium < 135mEq/L and increased serum lactic acid > 54.1mg/dl at hospital

admission has also been shown to increase mortality. Patients who showed an increase in

APACHE score between the 3rd and 7th postoperative day have poor prognosis. In

summary of the treatment options, we know that surgical debridement, rapid surgical

debridement, is important. Outcomes are based on the promptness of diagnosis, surgical

treatment, and the management of postoperative complications.

KEYWORDS

Necrotizing soft tissue infections (NSTI), Fournier's gangrene, Meleney's ulcers,

necrotizing fasciitis, sepsis, debridement, APACHE, LRINEC, GAS infections,

Hyperbaric oxygen therapy.

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NECROTIZING SOFT TISSUE INFECTIONS – A REVIEW

INTRODUCTION

Necrotizing soft tissue infections (NSTI) are certainly not new. They were first described

by Jones in 1871in the US Civil War as hospital gangrene related to group A beta-

hemolytic streptococci infections and Staphylococcus aureus [1]. Fournier has his name

stuck to Fournier's gangrene, after he described it in 1883 [2], and Meleney to Meleney's

ulcers, in 1924 [3]. The term "necrotizing fasciitis" was coined in 1952 by Wilson [4].

This is an evolving disease. Although it's not new, there are new challenges, in early

recognition of this disease and a holistic approach to reduce the mortality which still

remains high, ranging from 24% to 34%, and has not changed significantly for several

decades [5].

Definition and Nomenclature: is it really required?

Avery Nathens, has coined the concept of "debunking the nomenclature" in 2005. Really,

the nomenclature for any disease is helpful only if it changes the prognosis or treatment,

and this is really not true for necrotizing soft tissue infection. Hence, one should consider

NSTI as one entity “as any infection of the soft tissue that is associated with necrosis

requiring operative intervention and this usually occurs in the context of a critically ill

patient”.

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 Diagnosing Necrotizing Soft Tissue Infections

It is based on a constellation of symptoms, physical signs, and laboratory assessment. The

main symptom described is pain out of proportion to the physical findings; this can be

sometimes difficult to interpret, particularly if a patient is already far down their course

and not with a clear mental status. Initially, NSTI is manifested by severe pain localized

at the trauma site. However, this is disproportionate to the physical findings, as skin

usually doesn’t carry any infection signs. When skin is involved, it is red-bluish due to

vascular thrombosis. Fluctuation, tenderness and exudates, not necessarily malodorous or

purulent, might exist and skin is warm to palpation. Lymph node involvement may also

be seen, except in diffuse-type inflammations such as clostridium gangrene. In more

progressed cases, large haemorrhagic bullae, skin necrosis, sensory and motor deficits

and crepitus on palpation (hard signs). Inflammatory edema increases pressure in the

muscle compartments resulting in vascular thrombosis and leading to tissue ischaemia,

which triggers a new onset of infection and tissue necrosis. Systematic clinical

symptoms, such as hypotension, fever (temperature > 38°C), tachycardia, tachypnoea,

mental disturbance, tremor, and laboratory findings of marked increase in white blood

cell count and metabolic acidosis are advanced indices of development of sepsis. Early

diagnostic difficulties are attributed to the lack of cutaneous findings. Although a large

necrotic area shows bacterial aggressiveness and fast spread, it is a delayed manifestation.

A simple X-ray may demonstrate soft tissue gas, which implies mainly the existence of

anaerobic microbes; however, there are also aerobes producing gas. Computed

tomography (CT) and magnetic resonance imaging (MRI), demonstrate soft tissue gas as

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well as surrounding edema, but they are mainly indicated in order to define the extent of

the infection and the existence of retroperitoneal necrosis and should never delay

operative intervention [6, 7]. It has not been proven that the use of early MRI improves

the mortality and morbidity rate [8]. It cannot be overemphasized, however, that these

studies are only adjuncts in the evaluation of patients with potential NSTI and should not

be relied upon to exclude the diagnosis. The diagnosis is still primarily a clinical one.

Most important, the extent of debridement is determined by physical findings at the time

of surgery and not by CT/MRI findings. Some authors advocate the use of fine-needle

aspiration for diagnosing NSTI but this procedure has limited usefulness and can be

misleading. Occasionally, paracentesis, fluid aspiration and direct Gram stain help in the

appropriate antibiotic selection. A positive aspiration confirms infection, but a negative

examination does not exclude it. A more recent approach to the diagnosis of NSTI is

bedside incisional biopsy down to the fascial level. This biopsy is immediately sent for

frozen section culture and Gram stain. This analysis is far more accurate than that

performed on a fine-needle aspirate. Incisional biopsy appears to be the only reasonable

approach to the diagnosis other than a trip to the operating room. Also described in the

literature, is this concept of a finger test. It is infiltrating with local anesthetic; doing a 2-

cm incision down to the fascia looking for ominous signs, such as some thrombosis of the

microvasculature, dishwater fluid; or being able to push your finger along the deep fascial

planes.

Predictors of Mortality or Prognostic Factors

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According to most authors, quick and aggressive surgical treatment improves survival

compared to delayed surgical intervention. Wong et al. proved with the method of

multiple regression analysis that delay in surgical debridement of more than 24 h after

hospital admission was the single independent factor that influenced mortality [9]. Elliot

et al. showed that diabetes mellitus did not influence mortality until it was associated

with age > 60 years and the presence of acute renal insufficiency [10]. The degree of

body area involvement, incomplete surgical debridement, WBC >15400/cmm, serum

sodium < 135mEq/L and increased serum lactic acid > 54.1mg/dl at hospital admission

has also been shown to increase mortality [5]. Total NSTI mortality rate is reported to

reach 25– 36%but for gas gangrene is around 60%.Mortality rate of NSTI of the limbs is

thought by some to be much lower and by others not. Pessa and Howard noticed that

death occurred in patients who showed an increase in APACHE score between the 3rd

and 7th postoperative day [11]. There are other scoring systems like LRINEC

(Laboratory Risk Indicator for NSTI) a score based on laboratory values [12]. It has been

criticized as complicated and highly relying on the C-reactive protein.

During the first 10 days from initial surgical debridement, death is attributed to septic

shock and later is due to multiple organ insufficiency.

Bugs and Drugs

Predisposing factors of NSTI include advanced age, diabetes mellitus, malnutrition or

obesity, chronic alcoholism, drug abuse, corticosteroid use, immunosuppression, AIDS,

chronic obstructive lung disease (COPD) together with the chronic use of steroids,

serious trauma, and chronic venous or lymph insufficiency with tissue edema. The

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presence of a foreign body in combination with/or dead tissue formation, urgent and

extensive abdominal or perineal operations, as well as tissue ischemia (most often due to

tight sutures, haematomas, peripheral angiopathy, or irradiation and wide burns), are

considered to be local predisposing factors. Pathogenesis of severe NSTI is known to be

multibacterial. Infections, especially, in the abdominal wall and perianal area are

multibacterial with both aerobic and anaerobic Gram-positive and negative organisms.

However, infections in limbs are usually due to a single microorganism arising from the

skin flora such as Staphylococcus pyogenes. All tissues obtained at the time of initial

surgical debridement should be subjected to aerobic and anaerobic cultures and Gram

staining. Although the Gram stain has been suggested as a guide to initial antibiotic

therapy of NSTI, it is of limited value given the polymicrobial etiology of most cases.

Recently, Group A streptococcal GAS infections have received much attention recently as

etiologic agents of NSTI, referred to in the lay press as “flesh-eating bacteria” [13 – 17].

An important aspect of streptococcal NSTIs is that they can occur in otherwise healthy

people at any age and may cause rapid onset of shock and multiple-organ failure. They

may follow minor or major trauma, injection of illicit drugs, accidental needle sticks and

varicella infections in children and adults. Elderly individuals and patients with

underlying medical disease are at greater risk for serious GAS infections, necrotizing

fasciitis and shock. Necrotizing GAS infections may occur anywhere on the body,

including the trunk, extremities and even the periocular area. Streptococcal toxic-shock

syndrome is a complication of GAS infections. Cases of so called “toxic strep syndrome”

are most commonly associated with group A streptococci M1 and M3. Streptococcal

pyrogenic exotoxins which cause the rash of scarlet fever are also known to act as

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superantigens. It has been suggested that shock may be mediated by massive release of

cytokines such as tumor necrosis factor alpha and interleukin- 1 beta induced by

streptococcal pyrogenic exotoxin A (SPEA) and streptolysin O (SLO) [18].

Patients suspected of having NSTI should be started empirically on broad-spectrum

antibiotics covering the most commonly encountered pathogens. The most frequently

advocated antibiotic regimen includes ampicillin/ penicillin, gentamicin and anaerobic

coverage with either metronidazole or clindamycin. Penicillin-allergic patients may be

started on aztreonam or vancomycin in place of ampicillin. . There is experimental

evidence suggesting that penicillin may be less effective due to an “inoculum effect” of

large numbers of slower growing organisms with decreased expression of certain

penicillin-binding proteins [19]. Clindamycin, which works by inhibiting protein

synthesis, is not subject to such effects hence use of clindamycin is recommended for

clostridia coverage as well as a protein-synthesis inhibitor, where it reduces toxin

production and binds the toxin produced by clostridia as well. Gentamicin as gram-

negative coverage -- unless there is significant renal dysfunction, in which one can use a

fluoroquinolone.

Surgical Treatment

Once the diagnosis of NSTI is made, treatment should be instituted promptly.

Resuscitation, based on the clinical state of the patient, includes aggressive fluid

replacement to manage acute renal failure from ongoing sepsis and shock. Intravenous

antibiotics are given and appropriate measures are taken to maintain cardiac output and

pulmonary stability. Urine output should be monitored via an indwelling urinary catheter.

9
The patient should be brought to the operating room without unnecessary delay and

undergo aggressive and extensive operative debridement. The principle is wide

debridement of all necrotic tissue with decompression of fascial planes and may require

an amputation, which is a difficult decision to make at the first operation, but in many

circumstances can be lifesaving. The skin, soft tissue and muscle should be debrided until

there is no further evidence of infected tissue, based solely on the findings at surgery. The

first operative debridement is the most important one for the survival of the patient [9]. It

is preferable to remove more tissue than necessary than to leave any actively infected or

necrotic tissue. The patient should then be returned to the operating room 12 -24 hours

later to confirm that there has been no extension of the infectious process and to debride

any skin and soft tissue edges that have become desiccated. The total number of trips to

the operating room is based on the condition of the wound and whether the infection has

been adequately controlled. Once the infection is controlled, daily dressings can be done

at the bedside, with sedation. Split-thickness skin grafts can be used later to cover the soft

tissue defects once the infection has been eradicated. Only rarely are more extensive

procedures needed in the acute setting.

The role of amputation in controlling NSTI is controversial. If infection can only be

eradicated by amputation, it should be done promptly and without hesitation. Controversy

also exists concerning the role of colostomy in patients with perineal wounds. If there is

regular fecal contamination of the wounds, colostomy should be performed. Because

NSTI can involve the abdominal wall in the usual sites of colostomy placement, this

procedure should be performed only after control of the infection and in an uninvolved

area.

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Adjunctive Therapy

Intensive care unit (ICU) supportive cares to focus on things such as glycemic control

and nutritional support as these patients are hyper metabolic and have large wounds and

high-protein needs. While some authors have advocated the use of hyperbaric oxygen in

the treatment of NSTI, in addition to operative debridement, its usefulness is

controversial [10, 11, and 20]. It has never been shown to improve survival rates when

compared to standard operative and supportive therapy. Moreover, few institutions have

facilities for hyperbaric treatment and patients are often too ill to be transported there for

treatments. Other novel therapeutic adjuncts to surgical therapy in future are

Plasmapheresis, Intravenous Immunoglobulin and Activated Protein – C [21].

Conclusion

NSTIs are relatively common infections that often present for medical attention late in

their course. The diagnosis is often missed at initial presentation, allowing further

progression of the infectious process. Patients most commonly present with pain at a soft

tissue site, with erythema and tenderness. The diagnosis is made clinically based on the

visual findings in the infected area and by a high index of suspicion on the part of the

clinician. Laboratory tests and plain x-rays may support the diagnosis but are frequently

normal despite ongoing infection. CT and MRI are sometimes useful, but the critical

condition of the patient often precludes their use. They should not be relied upon to

exclude the diagnosis of NSTI if the diagnosis is suggested. Once the diagnosis has been

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made, the patient is stabilized and taken to the operating room for debridement. Surgical

debridement should be performed daily until the acute infection has been controlled. In

summary of the treatment options, we know that surgical debridement, rapid surgical

debridement, is important. Outcomes are based on the promptness of diagnosis, surgical

treatment and the management of postoperative complications. A multi-disciplinary team

of health-care personnel, including general surgeons, plastic surgeons, infectious disease

specialists, intensivists, rehabilitation staff and nursing staff, are needed to provide the

extensive resources and time it takes for patient recovery.

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16. Marshall DH, Jordan DR, Gilberg SM, et al. Periocular necrotizing
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 DOCUMENT OF CONSENT

Date: 05 Apr 2008

This is to certify that our contribution titled Necrotizing Soft Tissue Infections – A
Review
be hereby considered for publication in THE INDIAN PRACTIONER under the
section (2)

• Original Article
• Review
• Pictorial Quiz/CME
• Drug Review
• Letter to the Editor
• Case Report

Authors : _________________________
1. Maj. Amit Kumar Shah, MBBS, MS(Gen Surg),*
Assistant Professor
Department of Surgery,
Armed Forces Medical College,
Pune, Maharashtra, India - 411040
Tele: 91-20-26306016
Fax: 91-20-26363301
Mobile no: 91-9373308006
amit_akshatshah@yahoo.co.in

___________________________
2. Col. Rajan Chaudhry, MBBS, MS, DNB
Professor & Head of Department,
Department of Surgery,
Armed Forces Medical College,
Pune, Maharashtra, India - 411040

* Corresponding Author

15