Necrotizing Soft Tissue Infections

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 [email protected]

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

* 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

2

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.

3

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 betahemolytic 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”.

4

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 5

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 2cm 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

6

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 7

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

8

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 gramnegative 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.

10

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

11

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.

12

References 1.

Sutherland ME, Meyer AA. Necrotizing soft-tissue infections. Surg. Clin. North

Am. 1994; 74: 591–607. 2.

Fournier JA. Gangre’ne foudroyante de la verge. Semin. Med. 1883; 3: 345–7.

3.

Meleney FL. Hemolytic streptococcus gangrene. Arch. Surg. 1924; 9: 317–64.

4.

Wilson B. Necrotizing fasciitis. Am. Surg. 1952; 18: 416–31.

5.

Arezou Yaghubiian, Christian de Virgillio, Christine Dauphine, RJ Lewis,

Mathew Lin. Arch Surg. 2007; 142(9): 840-846 6.

Arslan A, Pierre-Jerome C, Borthne A. Necrotizing fasciitis: unreliable MRI for

disease in the preoperative diagnosis. Eur. J. Radiol. 2000; 36: 139–43. 7.

Yamaoka M, Furusawa K, Uematsu T, Yasuda K. Early evaluation of necrotizing

fasciitis with use of CT. J. Craniomaxillofac.Surg. 1994; 22: 268–71. 8.

Theis JC, Rietveld J, Danesh-Clough T. Severe necrotizing soft tissue infections

in orthopaedic surgery. J. Orthop. Surg (Hong-Kong). 2002; 10: 108–13. 9.

Wong CH, Chang HC, Pasupathy S, Khin LW, Tan JL, Low CO. Necrotizing

Fascitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003; 85(8): 1454-1460. 10.

Eliot DC, Kufera JA, Myers RA. Necrotizing soft tissue infections: risk factors

for mortality and strategies for management. Ann Surg. 1996; 224(5) : 672-683. 11.

Pessa ME, Howard RJ. Necrotizing fasciitis. Surg Gynecol Obstet 1985; 161:357

– 361. 12.

Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk

Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004; 32(7): 1535-1541. 13.

Weinbren MJ, Perinpanagayam RM. Streptococcal necrotizing fasciitis. J Infect

1992; 25:299 – 302. 14.

Donaldson PMW, Naylor B, Lowe JW, et al. Rapidly fatal necrotizing fasciitis

caused by Streptococcus pyogenes. J Clin Pathol 1993; 46:617 – 620. 15.

Chelsom J, Halstensen A, Haga T, Hoiby EA. Necrotising fasciitis

due to group A streptococci in western Norway: Incidence and clinical features. Lancet 1994; 344(8930):1111 – 1115. 13

16.

Marshall DH, Jordan DR, Gilberg SM, et al. Periocular necrotizing

fasciitis: A review of five cases. Ophthalmology 1997; 104:1857 – 1862. 17.

Kliska DL, Thiede B, Caracciolo J, et al. Invasive Group A Streptococcal

infections in North Carolina: epidemiology, clinical features, and genetic and serotype analysis of causative organisms. J Infect Dis 1997; 176:992 – 1000. 18.

Hackett SP, Stevens DL. Streptococcal toxic shock syndrome: Synthesis of tumor

necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O. J Infect Dis 1992; 165:879 – 885. 19.

Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J

Med 1996; 334:240 – 245. 20.

Riseman JF, Zamboni WA, Curtis A, et al. Hyperbaric oxygen therapy for

necrotizing fasciitis reduces mortality and the need for debridement. Surgery 1990; 108:847 – 850. 21.

Cainzos, Miguel; Gonzalez-Rodriguez, Francisco J.

Necrotizing soft tissue

infections. The surgical patient Current Opinion in Critical Care. 13(4):433-439, August 2007.

14

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 [email protected] ___________________________ 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