Skin and Soft Tissue Infection Update: Presentation, Diagnosis, and Syndrome-Specific Antibiotic Management
February 27, 2000
Skin and Soft Tissue Infection Update: Presentation, Diagnosis, and Syndrome-Specific Antibiotic Management
Part II: Diabetic Foot Infections, Necrotizing Soft Tissue Infections, and Toxic Shock Syndrome
Author: Charles Stewart, MD, FACEP, Emergency Physician, Colorado Springs, CO.
Peer Reviewer: David Robinson, MD, MS, Research Director and Assistant Professor, Department of Emergency Medicine, The University of Texas Houston Medical Center; Director, Diagnostic Observation Center, Memorial Hermann Hospital, Houston, TX.
Identifying skin and soft tissue infections that represent a serious threat to life or limb is frequently difficult. Infections that present with little more than cellulitis, for example, can produce systemic signs and symptoms caused by bacterial exotoxins. These toxic shock syndromes can result from infection with a variety of organisms, and the initial appearance of the skin and surrounding tissues usually fails to indicate which infections will remain locally contained, and which will produce serious systemic consequences such as coagulopathy, shock, and cardiotoxicity.
Although not common, necrotizing infections of the soft tissue can result in amputation and/or death if surgical debridement is not performed expeditiously. Once again, these infections may be very difficult to diagnose and require surgical exploration to confirm the presence of deep tissue infection with myonecrosis or fasciitis. Because multiple bacterial etiologies cause soft tissue infections—whether it be diabetic foot ulcers, necrotizing soft tissue infections, or gangrene—antibiotic therapy must be empiric and usually requires combination drug therapy.
With these problematic issues in focus, the purpose of part two of this two-part series is to present diagnostic and treatment protocols for the more serious spectrum of skin and soft tissue infections, emphasizing the need for surgical intervention and appropriate antimicrobial therapy.
— The Editor
Diabetic Foot Infection
Potentially serious and usually difficult to treat, infections of the lower extremity frequently are encountered in diabetic patients and are among the most common causes for hospital admissions of older, diabetic patients. Most of these individuals will be admitted for both diagnostic studies and parenteral antibiotic therapy. A wide range of aerobic and anaerobic bacterial species are responsible for these infections, and it is estimated that up to 20% of these patients have involvement of underlying bone.1
General Principles. The diabetic foot is susceptible to soft tissue infections because of three principal factors: 1) sensory neuropathy; 2) chronic ischemia; and 3) alteration of host defenses. The mere presence of a foot ulcer does not necessarily mean that it is infected.
The peripheral neuropathy associated with diabetes permits repeated painless trauma to pressure points on the foot. Over time, these mechanical factors contribute to ulceration. The prevalence of diabetic neuropathy increases with duration of the disease and is exacerbated by poor metabolic control of diabetes. Multiple studies show that those patients with neuropathy and loss of protective sensation of the foot are at greatest risk of amputation, serious infection, or delayed healing of ulcers.1
In addition, decreased circulation to the soft tissue plays a major role in the impairment of host defenses in the diabetic. Arterial insufficiency occurs in up to 60% of patients with non-healing ulcers, and about 50% of those who require amputation.2 The presence of peripheral vascular disease predisposes to infection and slows ulcer healing.
Patients with poorly controlled diabetes (i.e., elevated blood glucose and glycosylated hemoglobin levels) may also have impairment of polymorphonuclear leukocyte function. Chemotaxis, adherence, phagocytosis, and intracellular bactericidal activity are found to be depressed in this patient subgroup.2 Subsequent ulceration provides a pathway for secondary infection that is typically polymicrobial.
Presentation and Diagnosis. Diagnostic confirmation of soft tissue infection in the diabetic foot requires data gleaned from both the history and physical examination. Erythema and purulent drainage are characteristic findings of an infected diabetic foot ulcer. Since many of these patients have neuropathy, pain may not be present. Erythema, increased drainage, crepitance, and/or pain in the leg or ankle may be the signs of limb-threatening infections. It should be stressed that fever is frequently absent. However, unexplained hyperglycemia may offer an early clue to the presence of a serious soft tissue infection.
Minor foot infections are characterized by less than 2 centimeters of erythema surrounding the ulcer, they are superficial, and systemic signs are typically absent. If the patient has systemic signs, if there is extension of the cellulitis beyond the wound margins, or if there is full thickness ulceration, then the infection is serious. Other findings that suggest a poor prognosis are rapid progression, gangrene of the overlying tissues, or gas in the ulcer or wound—all of which are associated with life- or limb-threatening infection. Moreover, such comorbid conditions as renal failure, malignancy, malnutrition, obesity, cardiac disease, or immunosuppression should prompt placing the patient in a more serious category.
Most infections are polymicrobial, with an average of 2-6 aerobic and/or anaerobic organisms cultured from most diabetic wounds.3 Secondary infection is common. Culture of the base of the ulcer after the wound has been surgically debrided offers the best opportunity for identifying causative organisms.
From a diagnostic perspective, radiographs of the foot and soft tissues are important. Soft tissue films may demonstrate gas or spread of the infections along fascial planes, whereas bone abnormalities may suggest osteomyelitis, a diagnosis that is difficult to make in the diabetic patient.4 Nuclear scans are occasionally helpful.
Treatment. The two principal objectives of treatment include preventing spread of the infection and avoiding amputation. Control of diabetes, drainage of abscesses, and debridement of necrotic tissue are important components of therapy. Elevation of the limb can help decrease edema. The patient should always be counseled to avoid weight bearing.
Optimal antimicrobial therapy for diabetic foot infections is still a matter of clinical controversy. Because a wide variety of both anaerobic and aerobic bacteria have been implicated in these infections, broad-spectrum antibiotic therapy is appropriate. As rule, minor infections will require coverage for the aerobic gram-positive cocci. Clindamycin, cephalexin, or dicloxacillin are effective when aerobic gram-positive organisms predominate.
However, for infections that are potentially limb-threatening, multiple agents that provide coverage for gram-positive cocci, gram-negative aerobes, and anaerobic organisms are usually necessary. Intravenous therapy is preferred for initial treatment. Ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin combined with tazobactam, and cefoxitin are reasonable single agents. Ciprofloxacin is an excellent choice for diabetic foot infections, especially when gram-negative organisms predominate; when empiric coverage is started with ciprofloxacin, it is recommended that anaerobic coverage be added with clindamycin. Adding anaerobic coverage with such agents as ceftazidime or ofloxacin is an effective alternative. Clindamycin is usually used for this anaerobic coverage. After the patient’s wound has shown significant improvement, stepdown therapy to oral antibiotics may be used.
As emphasized, most patients with diabetic foot infections usually are hospitalized for intravenous antibiotics. However, there is a recent trend to use intravenous antibiotics on an outpatient basis. When this approach is selected, the patient must return for therapy once or twice daily. In selected patients, this method can both reduce costs and be more comfortable to the patient. It requires a responsible and compliant individual to whom detailed follow-up instructions are provided.
Noninflamed ulcers of the foot usually can be considered uninfected and, therefore, they may be treated successfully without antibiotics. This clinical distinction, however, may be difficult. Nevertheless, careful wound care and attempts to relieve mechanical pressures at the site of the ulcer are important therapeutic measures. Before discharging the patient, the emergency physician must ensure that the patient has adequate follow-up.
Finally, surgery can play an integral role in the treatment of diabetic foot ulcers. All necrotic and infected soft tissue must be debrided both to control infection and to promote subsequent healing. Diabetic patients with osteomyelitis may require complete resection of the affected bone—or intensive debridement of the affected bone—usually in combination with a prolonged course of antibiotics. Limb-sparing procedures are preferred for surgical therapy of this disease. Unfortunately, despite the best therapy, amputation may be necessary to control the infection. Of the approximately 125,000 lower extremity amputations performed each year, about 50% are directly attributable to diabetes.5
Systemic Manifestations of Soft Tissue Infections
A number of organisms—most notable among them, staphylococcal and streptococcal species—can produce systemic, life-threatening complications associated with soft tissue infection. These distal effects result from the expression of bacteria-mediated toxins, which produce myriad consequences, many of them suggestive of a specific etiologic diagnosis.
Staphylococcal Toxic Shock Syndrome. In addition to common superficial infections, staphylococci can cause focal, soft tissue infection associated with two distant tissue effects: 1) toxic shock syndrome (TSS); and 2) staphylococcal scalded skin syndrome. From a pathophysiological perspective, it has been documented that these staphylococci secrete exfoliating toxins A and B, which can produce both bullous impetiginous lesions and staphylococcal scalded skin syndrome. Other staphylococci may secrete toxic shock syndrome toxin-1 and enterotoxin B or C, which cause the systemic findings that characterize toxic shock syndrome.6
A high index of suspicion is necessary to make the diagnosis of toxic shock syndrome, a condition that usually begins with an acute onset of fever and a characteristic rash. Staphylococcal toxic shock syndrome often occurs in young women using superabsorbant tampons. Interestingly, the contaminating staphylococci originate not from the tampon, but from the patient’s fingers. The blood-saturated tampon merely serves as a culture media.
The hallmark rash of toxic shock syndrome is a widespread macular, erythematous rash similar in appearance to sunburn. Initially, the rash will involve the trunk, after which it will spread centrifugally to the arms and legs; the palms and soles may be affected. In addition, mucous membranes become hyperemic and may even ulcerate. Some patients may have conjunctivitis. Vomiting and diarrhea are common early systemic symptoms. In survivors, about 10 days to three weeks after the onset of the disease, the patient will have desquamation of the skin similar to severe sunburn. Potentially fatal complications include shock, renal failure, cardiac arrhythmias, disseminated intravascular coagulopathy, and respiratory failure.
Treatment consists of appropriate fluid resuscitation and, if required, pressor agents. The tampon must be removed and the area should be cultured. Cloxacillin or other anti-staphylococcal penicillin is effective for most patients. Since this disease is due to a secreted toxin, rather than invasive infection, antibiotics will prevent elaboration of additional toxin. Most clinicians advise the patient not to use tampons again.
Staphylococcal Scalded Skin Syndrome. Scalded skin syndrome often starts in a child with a bullous impetigo. The lesion begins as a vesicle, and then gradually enlarges into flaccid bullae that rupture. New bullae typically appear over the next 2-3 days, during which time hair and nails may also shed. Fever, skin tenderness, and a scarlatiniform rash are common. The exfoliation toxin can be also secreted by localized infection in the nasopharynx, umbilicus, or urinary tract. In some children, exposed dermal surfaces will weep, while fluid and electrolyte losses may lead to hypovolemia. Exposed surfaces may also serve as a portal for other infections. Most children recover in about 10 days if appropriately treated.
Scalded skin syndrome should be treated with parenteral antibiotics. In a community-acquired infection, beta-lactamase-resistant antibiotics are appropriate.When the infection appears to have been acquired in a hospital or extended care facility, methicillin-resistant Staphylococcus aureus should be considered and vancomycin is the drug of choice. Intranasal mupirocin may provide benefits by eliminating intranasal colonization.
Streptococcal Infections
Invasive streptococcal disease affects all ages from neonates to geriatric patients and can follow minor or major trauma. The leading foci of infection include the skin and soft tissues, although abdominal, pelvic, pharyngeal, mucosal, and sinus infections also can produce the disease. In the early 1900s, scarlet fever epidemics were associated with Streptococcus pyogenes strains that produced pyrogenic toxin A.6 Milder disease was reported with exotoxins B and C. A recent increase in type A exotoxin-producing streptococci has led to an epidemic of scarlet fever, streptococcal bacteremia, and a streptococcal deep soft tissue syndrome. Pyrogenic exotoxin B secretors with a more virulent type of M protein also has produced outbreaks of severe disease.
The streptococcal "toxic shock-like syndrome" (STSS) was first identified in 1983.7 Almost 70% of the patients diagnosed with this condition are female, with an overall mortality rate of 24%. Fortunately, the disease is uncommon, with fewer than 20 cases per 100,000 population in the United States.8
From a clinical perspective, streptococcal toxic shock syndrome presents with an acute onset and is extremely virulent, with death occurring within hours to days from refractory hypotension, lactic acidosis, intravascular coagulopathy, renal dysfunction, and respiratory failure. Many of these patients will initially have a minor, localized soft tissue infection. Presence of the full-blown syndrome is suggested when organ dysfunction is out of proportion to the extent of local signs and symptoms. Vomiting, fever, and diarrhea are common during the initial stages of illness.
Marked tachycardia is common, and initial therapy in the emergency department may erroneously be directed toward a cardiovascular cause of the acute deterioration.9 Inadequate treatment or misdiagnosis of this superficial infection may allow deep tissue invasion and subsequent progression despite antibiotic therapy. Endotracheal intubation is frequently required because of respiratory distress.
The clinical features and multisystem involvement produced by streptococcal disease are similar to those associated with staphylococcal toxic shock syndrome. However, unlike staphylococcal toxic shock syndrome, Group A streptococcal infections with toxic shock are associated with extensive soft tissue infection, bullae formation, and bacteremia. Of special concern is the finding that the fatality rate is more than five times that observed with staphylococcal toxic shock syndrome. (See Table 1.)
| Table 1. Case Definition for STSS41 |
| Isolation of group A Streptococcus: |
| • From a normally sterile site |
| • From a nonsterile site (throat, sputum, vagina, superficial skin lesion, etc.) |
| Clinical signs of severity: |
| Hypotension |
| BP < 90 mmHg in adults |
| < 5th percentile for children |
| Two or more of the following clinical signs: |
| 1. Renal impairment |
| • Creatinine greater than 177 micromoles/L ( > 2 mg/dL) |
| • Creatinine greater than twice upper limit of normal for age |
| • Twofold elevation over the baseline level |
| 2. Coagulopathy |
| • Platelets less than 100,000/mm3 |
| • Disseminated intravascular coagulopathy |
| 3. Liver involvement |
| • SGPT > 2 ´ normal |
| • Total bilirubin > 2 ´ normal |
| • Liver enzymes twice normal for age |
| • Twofold elevation of liver enzymes |
| 4. Adult respiratory distress syndrome |
| 5. Generalized erythematous macular-papular rash |
| 6. Soft tissue necrosis, including necrotizing fasciitis, myositis, or both |
The pathogenesis of this potentially devastating syndrome is related to the role of exotoxins produced by specific strains of Streptococcus pyogenes. These exotoxins act as "superantigens" that interact with T-lymphocytes and stimulate mononuclear cells. The exotoxins stimulate monocytes to produce tumor necrosis factor alpha (TNF-alpha), interleukin-1-beta, and interleukin-6 (IL-6).8 These substances are potent mediators of fever, shock, and tissue injury associated with streptococcal toxic shock syndrome. In addition, these exotoxins have been found to be cardiotoxic, which may explain the acute, reversible cardiomyopathy encountered in many patients.9
The superantigen effect occurs because the exotoxins react with all T cells containing antigens to the T-cell receptors. In contrast, conventional antigens will react with only about 0.01% of T cells. This means that massive numbers of T cells release lymphokines, including TNF-beta, IL-2, and interferon. The magnitude of this antigen response may explain the enhanced virulence of the strains of streptococci that cause STSS.
Treatment of STSS includes aggressive supportive care and high-dose penicillin or clindamycin. In recent studies, some patients have not responded as well to penicillin, which has led authorities to suggest that clindamycin may be more effective.10 Patients with penicillin allergy should receive clindamycin. In the clinically septic patient, broad-spectrum antibiotics should be employed initially, since mixed infections can have a similar picture.
Unusual Soft Tissue Infections
Necrotizing Soft Tissue Infections. Necrotizing soft tissue infections are grave conditions usually not encountered in the day-to-day practice of emergency medicine. However, when they do present in the emergency department setting, these infections present a diagnostic and therapeutic challenge, both because they are uncommon and because the early manifestations are subtle. An ill-defined area of erythema and swelling characterizes the initial stages. The disproportionate pain and tenderness may be the only early clue to the severity of the disease process. By the time bullae, ecchymosis, and cutaneous necrosis produce the characteristic findings, the patient may have systemic toxicity or even shock.
Many authors have classified these infections into subgroups based on retrospective groupings of ill-defined anatomic structures, infecting organisms, or clinical presentation. Unfortunately, many bacteria can produce infections that have a similar clinical appearance and the results of culture are not often available to the emergency physician. Even infections that involve several soft tissue components can produce similar, initial clinical appearances, and therefore, offer little help to the emergency physician for prospective management of the patient.11 Finally, none of the classifications appear to influence subsequent therapy and outcome.12
With these limitations in mind, three common subgroups of necrotizing soft tissue infections will be discussed: 1) necrotizing fasciitis; 2) necrotizing cellulitis; and 3) myonecrosis. The emergency physician should always keep in mind that these descriptions are mostly retrospective and the same initial therapy is required for all three subgroups. (See Table 2.)
| Table 2. Clinical Signs Associated with Necrotizing Soft Tissue Infections |
| • Skin erythema, edema, warmth |
| • Blue, purple, or brown skin discoloration |
| • Skin necrosis and gangrene |
| • Bullae |
| • Subcutaneous crepitus |
| • Cutaneous numbness in the area of involvement |
| • Shock |
Whatever term is used for these infections, the common factor that improves survival is rapid recognition of tissue necrosis and prompt surgical debridement.13 A therapeutic protocol for the emergency physician should include systemic antibiotics, fluid resuscitation, and prompt surgical consultation for debridement. These patients should always be admitted to a surgical service, as surgical debridement is mandatory for patient survival.
Necrotizing Fasciitis. The term necrotizing fasciitis is used to describe a severe, acute life-threatening inflammatory condition caused by streptococcal or mixed bacterial infection. As the name implies, fasciitis spreads along fascial planes. The infection may involve the soft tissue layers of the pelvis, abdomen, extremities, or other sites. In most patients, very minor superficial epidermal or mucosal foci act as a portal of entry. Fasciitis can be caused by a single organism such as Streptococcus pyogenes, Clostridial species, Vibrio vulnificus, or by a combination of bacteria. When muscle is involved, the term "bacterial myonecrosis" is used.
The disease was first described in 1871, during the Civil War. Several synonyms for necrotizing fasciitis have been used, including hospital gangrene, gangrenous ulcer, putrid ulcer, phagedena (and phagedenic) ulcers and phagedena gangrenosa), and malignant ulcers. The term necrotizing fasciitis was first used in 1953 to describe the classic lesions that encompass all of these diseases.
In 1883, Fournier described the gangrene of the scrotum that bears his name.14 Fournier’s gangrene is a variant of necrotizing fasciitis that starts in the perineum and genitalia. As described by Fournier, the hallmarks of the infection were an abrupt onset, a rapid progression to frank gangrene, and an idiopathic etiology. The scrotum readily develops dermal gangrene in the presence of necrotizing fasciitis because there is no subcutaneous fat layer between the dartos fascia and the epidermis. The pathologic processes are identical to other forms of necrotizing fasciitis.
Pathology. In necrotizing fasciitis, there is separation between and infection of the overlying skin and subcutaneous tissue. Typically, the infection causes thrombosis of the nutrient vessels, fat necrosis, and inflammation. The fascia appears gray and stringy rather than the usual pink, firm tissue. The fascia separates from the underlying tissue, and an instrument can be passed easily along the deep fascial planes. The affected tissue may be cultured to make an etiologic diagnosis, which may consist of one or more organisms.
The three predominant aerobes are Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli. Anaerobic bacteria outnumber aerobes at all sites, but predominate in the buttocks, inguinal area, genitalia, and the trunk. The major anaerobes include Peptostreptococcus species, Bacteroides fragilis, the Clostridium species, and lesser-known Prevotella and Porphyromonas species. Rarely, Pasturella multocida and Streptococcus pneumoniae can cause necrotizing fasciitis.15 These organisms can produce toxins and enzymes that cause tissue necrosis, destroy proteins, and terminate in septic shock. At the primary site of the infection there is fascial necrosis with infiltration of inflammatory cells and fibrinoid necrosis of both arterial and venous walls. The resulting thrombosis causes the skin breakdown.
Vibrio. Halophilic bacteria found in seawater can cause a fulminating infection after only brief exposure to the marine environment. Vibrio species, particularly V. vulnificus, are responsible for this necrotizing fasciitis.16,17 Indeed, once skin necrosis occurs with Vibrio species infections, there may not be enough time to debride the wound before there is rapid progression of sepsis, shock, and death. The only predictor of increased risk from skin necrosis and death is the presence of significant chronic illness. This infection responds poorly to antibiotics alone, and the initial appearance is indistinguishable from other causes of necrotizing fasciitis. Timely operative exploration and debridement will improve survival and decrease hospital stay in survivors.
Group A Streptococci. Necrotizing fasciitis caused by group A streptococci has received increasing attention by the media in recent months. The British press coined the term "flesh eating bacteria" in 1994 to describe an outbreak in Gloucestershire, England.18 The six cases reported in Gloucestershire were caused by four different strains of bacteria and thus were only happenstance.
A number of predisposing conditions to streptococcal necrotizing fasciitis include varicella, minor trauma, and childbirth. The rapid spread of group A streptococcal necrotizing fasciitis may cause death before a diagnosis has been made. Group A streptococcal infection is often accompanied by the streptococcal toxic shock syndrome as described above. Pyrogenic exotoxin A is thought to be the mediator of the toxic shock syndrome. Most patients not only have deep infection, but also hypotension, renal dysfunction, and respiratory failure.
Clinical Presentation and Diagnosis. Necrotizing soft tissue infections may follow soft tissue trauma, circumcision, postoperative infections, subcutaneous injections, cutaneous infections, ulcers, acupuncture, perirectal abscesses, strangulated hernias, insect bites, phymosis, paraphymosis, injection of illegal drugs, and idiopathic infections. There are few, definitive clinical symptoms and signs that point to an early diagnosis of this condition. However, the presence of risk factors in a patient with "simple cellulitis" or a suspicious lesion should prompt the emergency physician to consider the possibility of necrotizing soft tissue infection. (See Table 3.) When faced with the dilemma of differentiating simple cellulitis from an occult deep soft tissue infection, the physician’s clinical suspicion should prompt early consultation with a surgeon.
| Table 3. Risk Factors Associated with Necrotizing Skin Lesions19 |
| • Compromised immune status 20 |
| • Age older than 50 years |
| • Diabetes mellitus |
| • Arteriosclerosis |
| • Malnutrition |
| • Alcoholism |
| • Obesity |
| • Intravenous drug abuse |
| • Renal failure |
| • Trauma |
| • Malignancy |
| • Varicella infection 21 |
The involved area is initially swollen without well-defined margins, hot, tender, and erythematous. Inflammatory changes of the skin are common, but necrosis or bullae of the skin is found in only one-third of the patients who subsequently are found to have necrotizing fasciitis. Perhaps, severe pain out of proportion to the size and type of the wound is the most important symptom. Nonspecific signs, such as fever and tachycardia, are common.
The infection progresses over hours and the skin changes from erythematous to dusky or purplish with widespread erythema and edema. Skin breakdown follows with bullae and skin necrosis. The involved area becomes anesthetic due to destruction of skin, blood vessels, and superficial nerves. General systemic signs become more severe and the patient may have profound tachycardia, tachypnea, oliguria, and hypotension. Septic shock will follow as necrosis spreads through subcutaneous fat, muscle, and fascia.
A radiograph of the affected area should be obtained to look for soft tissue gas. The absence of soft tissue gas does not rule out a necrotizing deep soft tissue infection. When identified, however, this finding mandates rapid surgical exploration. Computed tomography, ultrasound, or MRI may be helpful in the diagnosis of patients with early signs, but should never delay immediate surgical exploration in patients with obvious findings.22-25 Fine needle aspiration may demonstrate either pus or bacteria in the Gram’s stain of the aspirate. Unfortunately, this procedure is positive in only about 80% of cases of necrotizing fasciitis.22
Surgical exploration is the definitive diagnostic technique. The surgeon should proceed with operative wound exploration when the clinical symptoms are inconsistent with the skin findings, when cellulitis does not rapidly respond to antibiotic treatment, or when the patient appears to have system toxicity from a cellulitis. During exploration, Gram’s stains or tissue biopsy with frozen section analysis can confirm the disease process.
Prognosis. Despite dramatic improvements in the management of many infectious diseases, the mortality and morbidity of these necrotizing infections is significant. This may be due to difficulty in making the diagnosis and failure to institute rapid therapy. The reported mortality rate of necrotizing fasciitis is about 40%.22 This high mortality rate is often attributed to overwhelming sepsis and multisystem organ failure. The patient may also have such complications as disseminated intravascular coagulopathy, renal failure, and hemolysis. Major factors associated with higher mortality rates include failure to promptly recognize the disease, failure to appreciate the extent of the necrotizing process, delay in debridement, and co-existing diseases. If the patient presents with excruciating pain and signs of systemic toxicity, then the physician must be aware that extensive necrosis may be present despite only modest symptoms visible on the skin examination.26
Close monitoring of the patient for progressive skin changes may permit an early diagnosis. These changes may include edema, erythema, crepitus, or diffuse spreading cellulitis. Worsening of pain and deterioration of the patient’s condition demands prompt surgical exploration.
Surgical Management. Treatment of necrotizing fasciitis is rapid surgical debridement of the necrotic tissue in addition to intravenous antibiotics that are sufficiently broad in spectrum to cover the most likely organisms. Aggressive fluid resuscitation may be needed. Tetanus immunization should be brought up to date.
Because necrotic tissue cannot be salvaged and the bacteria located in necrotic areas are beyond the reach of intravenously delivered antibiotics, debridement is the mainstay of therapy. Multiple debridements are usually necessary because of the patient’s condition and the rapid spread of the disease.27
Debridement should not be delayed because the patient is in shock.28 Time is a critical element in the management of these patients, and delays in debridement must be avoided. Since the testes have their own blood supply and are only rarely compromised by Fournier’s gangrene, it is generally accepted that they should not be removed.29,30
Antibiotic Therapy. An appropriate antibiotic regimen must be started immediately. While cultures are pending or when the Gram’s stain is inconclusive, broad-spectrum antibiotics are appropriate. For an infection in the perineum, coverage must include Enterococcus and Enterobacteriacea, as well as anaerobic bacteria found in the large bowel. This may require a combination of ampicillin-sulbactam, gentamicin, metronidazole, and perhaps, clindamycin. The increase in beta-lactamase-producing bacteria, particularly Staphylococcus aureus, has important implications for antimicrobial therapy.31 Beta-lactamase inhibitors such as clavulanic acid or sulbactam provide additional coverage.
If the cause is thought to be group A streptococcus, then clindamycin or penicillin is appropriate. Clindamycin may be more effective than penicillin. Acceptable alternative therapy would be a broad-spectrum cephalosporin with appropriate activity for mixed aerobic and anaerobic bacteria. Piperacillin combined with tazobactam will cover most bacteria associated with skin infections.32 Quinolones have less activity against aerobic streptococci and Staphylococcus aureus.33 They are not approved for use in children.
Hyperbaric Oxygenation. Use of hyperbaric oxygenation (HBO) for treatment of necrotizing infections is controversial. The theory is that hyperbaric oxygen will kill or at least immobilize anaerobic microbes. Since blood flow to the area is impaired, the hyperbaric oxygen provides diffusion flow to the necrotic areas. The effectiveness of HBO in some studies has not been shown to be statistically significant.34 The studies have had a small number of patients, and are often not randomized.
Certainly, if HBO is readily available in the hospital or local community, it is a reasonable option for most patients. When it is not available, the hemodynamically unstable patient may be quite difficult to transport to a distant facility with HBO. It is unclear whether the hazards of transport will provide significant benefit over local surgical debridement and antibiotics. The use of HBO delays surgical debridement.
Meleney’s Synergistic Gangrene. Gangrene of the skin associated with an underlying infection is caused by vascular thrombosis in the subcutaneous tissues, fascia, or muscle. Since vascular thrombosis can be caused at all three levels, gangrene is not diagnostic of an infection at any single level. However, gangrene of the skin does mandate further investigation.
Meleney’s synergistic gangrene is an ulcerating necrotic lesion of the skin and immediate subcutaneous tissues caused by the synergistic action of Staphylococcus aureus and hemolytic streptococci such as group A streptococcus or Streptococcus pyogenes.35 It is characterized by widespread superficial and fascial necrosis. This disease has also been called postoperative progressive gangrene, progressive bacterial synergistic gangrene, gangrenous erysipelas, or necrotizing erysipelas.
It most often occurs at an operative site, often originating at wire retention sutures. Penetrating injuries and bedsores are other sites for the infection.
Treatment includes antibiotics and removal of the retention sutures. Wide surgical excision of the lesions may also be required.
Bacterial Myonecrosis. The other deep necrotizing soft tissue infection is bacterial myonecrosis. An uncommon disease, bacterial myonecrosis has a grave prognosis even with appropriate and aggressive therapy. In many studies, the mortality exceeds 75%.26 From a clinical perspective, bacterial myonecrosis is a dramatic infection with rapid spread, severe local pain, and extreme systemic toxicity. Like necrotizing fasciitis, the patient may have skin discoloration, edema, bullae, or frank skin necrosis. As the name implies, myonecrosis involves the muscle. The term "gas gangrene" should be abandoned, since gas in the tissues is not necessary for the disease and gas in the tissues can be caused by other conditions.
The same organisms that cause necrotizing fasciitis have been implicated in non-clostridial myonecrosis.36 Clostridial infections may be caused by C. perfringens, C. novyi, or C. septicum. Patients with an occult malignancy are at increased risk for infection with C. septicum, although there is no known reason for this association. There is little difference in the clinical presentation or risk factors between myonecrosis and necrotizing fasciitis as discussed above. Systemic findings may be more frequent and more severe than those seen with necrotizing fasciitis. They may include diaphoresis, fever, profound tachycardia, and toxic delirium. The patient’s skin may turn bright orange or magenta.
Patients at risk for myonecrosis include trauma victims with contaminated wounds. When clostridia are inoculated into normal muscle, they are unable to germinate because of the high oxygen tension. In the traumatized or ischemic wound, clostridia spores germinate and grow. In clostridial myonecrosis, a rapidly spreading skeletal muscle infection is caused by toxin-producing clostridia, which are often associated with gas production in the muscle. The most important clostridial toxins include alpha-toxin and theta-toxin. These toxins destroy white blood cells and promote spread of the infection.
Alpha-toxin destroys lecithin and subsequently causes cell wall rupture. Permeability of the surrounding capillaries is affected, allowing massive local edema to form. Alpha toxin is also thought to cause histamine release, platelet aggregation, and thrombus formation. Alpha-toxin may be cardiotoxic through inhibition of the calcium channel pump in the sarcoplasmic reticulum of the heart muscle.
Theta-toxin is cardiotoxic and may cause cardiac failure or cardiogenic shock. Theta-toxin also causes platelet aggregation.37 Tissue necrosis and hemolysis are common.
Hypovolemic shock with cardiac failure, hemolysis, jaundice, acute renal failure, gastrointestinal hemorrhage, and severe respiratory distress are often found with myonecrosis. The resulting multisystem failure and rapid demise is a common outcome in myonecrosis. Mortality rates range from 20% to greater than 70%.37 The high mortality results from the combined and often irreversible problems of myocardial depression, septic shock, and multisystem failure.
Diagnosis. A presumptive diagnosis may be made by a Gram’s stain of fine needle tissue aspirate. The Gram’s stain usually shows the typical gram-positive rod. Few white blood cells are found in the discharge. Myonecrosis can also occur with other organisms, including Group A streptococci and anaerobic streptococci.
A radiograph of the underlying tissues for the presence of gas should be obtained. Subcutaneous gas is not diagnostic for clostridial myonecrosis. Although clostridial myonecrosis is generally the best known gas gangrene, in fact, the majority of gas-producing soft tissue infections are caused by facultative bacteria (E. coli, Klebsiella, and Proteus), Enterobacteriaceae species, or a variety of anaerobic bacteria.38,39 Rarely, gas can be found with streptococcal infections. A foul odor is most often associated with infection by Bacteroides species.
Since necrotic tissue is found in the presence of subcutaneous air, this is an absolute indication for surgical exploration. The most definitive diagnostic test is surgical exploration to define the extent of the infection and the tissues involved. If there is any question about the clinical diagnosis in the patient at risk, then surgical exploration is indicated. At the time of surgical exploration, the muscle involved is visibly edematous, pallid, and fails to contract when stimulated. A thin, watery discharge may be noted. Late findings include blackened, necrotic muscle. The involvement can be extensive, extending well beyond the skin involvement.
Management. Surgical therapy includes debridement of the devitalized tissue, drainage of loculations, and removal of clots and foreign debris. Radical debridement of the muscle is often necessary. Antimicrobial therapy is identical to that used for necrotizing fasciitis. Penicillin has been the drug of choice for clostridia, although some strains are beginning to show decreased sensitivity to this antibiotic.
HBO can be considered, as it is bacteriostatic to anaerobic organisms, in general, and clostridia, in particular. As noted earlier, it may hinder the production of some exotoxins. Administration of HBO oxygenation should never delay surgical treatment of this disease.40
References
1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986.
2. Caputo GM, Joshi N, Weitekamp MR. Foot infections in patients with diabetes. AFP 1997;56:195-202.
3. Lipsky BA, Baker PD, Landon GC, et al. Antibiotic therapy for diabetic foot infections: Comparison of two parenteral-to-oral regimens. Clin Infect Dis 1997;24:643-648.
4. Lipsky BA, Pecoraro RE, Wheat LJ. The diabetic foot: Soft tissue and bone infection. Infect Dis Clin North Am 1990;4:409-432.
5. Armstrong DG, Lavery LA, Quebedeaux Tl, et al. Surgical morbidity and the risk of amputation due to infected puncture wounds in diabetic vs non-diabetic adults. South Med J 1997;90:321-389.
6. Hill MK, Sanders CV. Skin and soft tissue infections in critical care. Crit Care Clin 1998;14:251-262.
7. Sutherland ME, Meyer AA. Necrotizing soft tissue infections. Surg Clin North Am 1994;74:591-606.
8. Lewis RT. Soft tissue infections. World J Surg 1998;22:146-151.
9. Forni AL, Kaplan EL, Schlievert PM, et al. Clinical and microbiological characteristics of severe group A streptococcus infections and streptococcal toxic shock syndrome. Clin Infect Dis 1995;21:333-340.
10. Wolf JE, Rabinowitz LG. Streptococcal toxic shock-like syndrome. Arch Derm 1995;131:73-77.
11. Hsiao GH, Chang CH, Hsiao CW, et al. Necrotizing soft tissue infections: Surgical or conservative treatment? Derm Surg 1998;24:243-248.
12. Freischlag JA, Ajalat G, Busuttil RW. Treatment of necrotizing soft tissue infections: The need for a new approach. AM J Surg 1985;149:751-755.
13. Iorianni P, Oliver GC. Synergistic soft tissue infections of the perineum. Dis Colon Rectum 1992;35:640-644.
14. Fournier JA. Gangrene foudroyante de la verge. Sem Med 1883;3:345-348.
15. Kragsbjerg P, Noren T, Soderquist B. Deep soft tissue infections caused by Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis 1995;14:1002-1004.
16. Howard RJ, Pessa ME, Brennanman BH, et al. Necrotizing soft-tissue infections caused by marine vibrios. Surgery 1985;98:126.
17. Halow KD, Harner RC, Fontenelle LJ. Primary skin infections secondary to Vibrio vulnificus: The role of operative intervention. J Am Coll Surg 1996;183:329-334.
18. Moses AE. Necrotizing fasciitis: Flesh-eating microbes. Isr J Med Sci 1996;32:781-784.
19. Bosshardt TL, Henderson VJ, Organ CH. Necrotizing soft-tissue infections. Arch Surg 1996;131:846-854.
20. Wolfson JS, Sober AJ, Rubin RH. Dermatologic manifestation of infections in immunocompromised patients. Medicine 1985;64:115-133.
21. Waldhausen JHT, Holterman MJ, Sawin RS. Surgical implications of necrotizing fasciitis in children with chickenpox. J Ped Surg 1996;31:1138-1141.
22. Lille ST, Sato TT, Engrav LH, et al. Necrotizing soft tissue infections: Obstacles in diagnosis. J Am Coll Surg 1996;182:7-11.
23. Kaplan DM, Schulman H, Fliss DM., et al. Computed tomographic detection of necrotizing soft tissue infection of dental origin. Ann Otol Rhinol Laryngol 1995;105:164-166.
24. Loyer EM, DuBrow RA, David CL, et al. Imaging of superficial soft tissue infections: Sonographic findings in cases of cellulitis and abscess. AJR 1996;166:149-152.
25. Schmid MR, Kossman T, Duewell S. Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR 1998;170:615-620.
26. Ben-Aharon U, Borenstein A, Eisenkraft S, et al. Extensive necrotizing soft tissue infection of the perineum. Isr J Med Sci 1996;32:745-749.
27. Riseman JA, Zamboni WA, Curtis A, et al. Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. Surgery 1990;108:847-850.
28. Bosshardt TL, Henderson VJ, Organ CH. Necrotizing soft tissue infections. Arch Surg 1996;131:846-854.
29. Kearny GP, Carling PC. Fournier’s gangrene: An approach to its management. J Urol 1983;130:695-698.
30. Biwas M, Godec C, Ireland G, et al. Necrotizing infection of scrotum. Urology 1979;14:576-580.
31. Blumer JL, O’Brien CA, Lemon E, et al. Skin and soft tissue infections: Pharmacologic approaches. Pediatric Infect Dis 1985;4:336-341.
32. File TM, Tan JS. Treatment of skin and soft-tissue infections. Am J Surg 1995;169(5A Suppl):27S-33S.
33. Brook I. Antimicrobial therapy of skin and soft tissue infection in children. J Am Pod Med Assn 1993;83:398-405.
34. Brown DR, Davis NL, Lepawsky M, et al. A multicenter review of the treatment of major truncal necrotizing infection with and without hyperbaric oxygen therapy. Am J Surg 1994;167:485-489.
35. Simmons RL, Ahrenholz DH. Infections of the skin and soft tissues. In: Howard RJ, Simmons RL (eds): Surgical Infectious Diseases, 2nd Ed. Norwalk CT; Appleton & Lange: 1988;377.
36. Ahrenholz DH. Necrotizing soft tissue infections. Surg Clin North Am 1988;68:199-214.
37. Redfield D, Hayes T. Orthopedic infections. Crit Care Nurs Q 1998;21:24-35.
38. Moses AE. Necrotizing fasciitis: Flesh-eating microbes. Isr J Med Sci 1996;32:781-784.
39. Dellinger EP. Severe necrotizing soft-tissue infections. JAMA 1981;246:1717-1721.
40. Sutherland ME, Meyer AA. Necrotizing soft tissue infections. Surg Clin North Am 1994;74:591-606.
41. Schurr M, Engelhardt S, Helgerson R. Limb salvage for streptococcal gangrene of the extremity. Am J Surg 1998;175:213-217.
Physician CME Questions
33. Arterial insufficiency is seen in what percentage of diabetic patients with non-healing ulcers?
A. 10%
B. 30%
C. 60%
D. 90%
34. When gram-negative organisms predominate, what is a good antibiotic choice for diabetic foot infections?
A. Clindamycin
B. Metronidzole
C. Ciprofloxacin
D. Cephalexin
35. What percentage of lower limb amputations are attributable to diabetes?
A. 10%
B. 20%
C. 30%
D. 40%
E. 50%
36. The dermatologic hallmark of toxic shock syndrome consists of:
A. bullous lesions.
B. vesicles on palms and soles.
C. widespread macular, erythematous rash.
D. lymphangitis.
37. What percentage of patients with streptococcal toxic shock-like syndrome (STSS) are females?
A. About 20%
B. About 30%
C. About 50%
D. About 70%
38. The pathogenesis of STSS is related to exotoxins.
A. True
B. False
39. The three predominant aerobic organisms causing necrotizing fasciitis include:
A. Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli.
B. Bacteroides, Klebsiella, and Prevotella.
C. Pasturella multocida, Klebsiella, and Pseudomonas.
D. none of above.
40. Hypberbaric oxygen treatment for necrotizing infections is controversial.
A. True
B. False
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