SUPERFICIAL INFECTIONS

Superficial infections are limited anatomically to the epidermis and the dermis. These infections can occur spontaneously or secondary to minor trauma. Impetigo usually presents with vesicles that leak, producing a thick yellow crust. These lesions are typically located on the face, neck, and extremities. Staphylococcus aureus and Streptococcus pyogenes are the most common causative agents. Bullous impetigo, like impetigo, is most commonly caused by S. aureus. It is characterized by small vesicles that coalesce to form large bullae.

Folliculitis develops as an infection of the hair follicle. The lesions appear as pustules or papules, commonly on the extremities, scalp, or beard. Whirlpool folliculitis is associated with immersion in inadequately chlorinated pools, whirlpools, or hot tubs. Diffuse pustules are seen. Pseudomonas aeruginosa is the classic causative agent. Swimmer’s itch is a folliculitis that develops after freshwater exposure.

Furuncles, deeper inflammatory nodules, can develop from folliculitis. S. aureus is often the causative agent. Carbuncles are coalescing furuncles formed by connecting sinuses. The nape of the neck is the most common anatomic location. S. aureus is most often isolated. Patients often have comorbidities such as diabetes mellitus, alcoholism, immunosuppression, or malnutrition. Systemic infection may result from these lesions.

Cellulitis is an inflammation of the subcutaneous tissue. There is erythema, pain, and edema of varying severity. A portal of entry for the bacteria is usually present. It may be as mundane as a crack in the skin from dryness or athlete’s foot. More substantial trauma may be involved, such as shotgun or shrapnel penetrations. Systemic symptoms may manifest and include fever, chills, malaise, and (infrequently) organ failure. Streptococcus (Groups A, B, C, and G) as well as staphylococcus are frequent culprits. Areas of compromised venous or lymphatic drainage are prone to this infection, and recurrence is common. Pelvic radiation or having had lymphadenectomy, mastectomy, or venectomy makes the development of cellulitis more likely.

DEEP INFECTION

Deeper infections are more frequently life- and limb-threatening. The literature concerning the potentially life-threatening infections is confusing. Multiple terms are used to describe the same disease, depending on the clinical setting in which it arises. The treatment is the same regardless of the term used to describe it. It therefore seems that anatomic classification is more logical and easily remembered. This review uses anatomic characterizations and relate them to older terminology as necessary.

In the medical literature, deep structure infection has masqueraded under a variety of pseudonyms. The term “necrotizing soft tissue infection” (NSTI)is used here. Table 1 lists a variety of terms that may appear in the medical literature to describe this infective process.

Table 1 Terms Used to Describe NSTI

All the terms describe an infection involving the subcutaneous fat and fascia, with variable skin involvement. The incidence of this infection is not known. A recent report quotes World Health Organization statistics of 500–1500 cases of necrotizing fasciitis annually. Though uncommon, it is not rare. The Centers for Disease Control has monitored Group A streptococcal infections and estimated 10–20 cases per 100,000 population. In Ontario, Canada, a population study estimated an incidence of 0.6 per 100,000.

CLINICAL PRESENTATION

Signs and symptoms of NSTI can be quite nonspecific (Table 2). Pain, erythema, and swelling of the affected area are most frequently present. This same constellation of symptoms may be seen in pathologic processes that have a much more benign course and respond effectively to antibiotic therapy alone. “Hard signs” of necrotizing infection include tense erythema, bullae, skin discoloration, and crepitus, pain out of proportion to examination, or anesthesia of the affected area. Unfortunately, many of these are late signs and indicate that the infective process is well established or they occur only in a small percentage of patients.

Signs of systemic toxicity may also be present. These may include pyrexia, tachycardia, hypotension, and organ dysfunction. The progression of symptoms may be rapid over the course of hours to days or more indolent over the course of days to weeks. The rate of progression of symptoms may be ameliorated by partial treatment. Some suggest classifying the disease by its clinical course. Fulminant disease presents in patients with acute onset and rapid progression over the course of hours with shock. Acute disease presents with large surface area involvement and over the course of days. Subacute disease presents for weeks and is usually localized. Differentiating this process from cellulitis or simple abscess can be a challenge. Clinically, failure to improve with appropriate antibiotics or worsening systemic toxicity portends this diagnosis (Table 3).

Table 3 Bacteriology

Laboratory data are equally nonspecific. Leukocytosis, hyponatremia, and elevated creatinine phosphokinase have been evaluated in clinical studies and may be markers of the disease. Wall et al. matched 21 patients with necrotizing fasciitis with controls and attempted to identify parameters that would distinguish the groups. White blood cell count (WBC) > 15.4 × 10⁹/l, serum sodium (Na) less than 135 mmol/l, or both, were the best factors to distinguish necrotizing fasciitis from non-necrotizing fasciitis. The sensitivity was 90%, and the specificity was 76%. In this study, 40% of the patients with necrotizing fasciitis lacked “hard signs.” Wong and colleagues developed the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score. The score was developed retrospectively based on WBC, hemoglobin (Hgb), serum Na, C-reactive protein, creatinine, and glucose in patients with necrotizing fasciitis and patients with other severe soft tissue infections. A score of ≥6 had a positive predictive value of 92% and a negative predictive value of 96%. In a cohort of prospectively evaluated patients, the model was found to have a positive predictive value of 40% and a negative predictive value of 95%. Creatinine phosphokinase (CPK) elevation was found by one group to distinguish patients with group A streptococcal necrotizing fasciitis (GAS) from non–group A streptococcal necrotizing fasciitis. CPK elevations were >600 IU/l in the GAS group.

DIAGNOSTIC IMAGING

Diagnostic imaging may be useful in diagnosis or in defining the extent of disease. The hallmark of necrotizing, air in subcutaneous tissues, can be seen with a variety of imaging techniques. Plain radiographs will demonstrate subcutaneous air in only 16% of patients. Plain films may also demonstrate foreign bodies. This is especially important when treating intravenous drug users. Ultrasonography, computed tomography (CT scan), and magnetic resonance imaging (MRI) are more sensitive than plain radiography in demonstrating air in the tissues. These modalities may additionally identify fluid collections in the subcutaneous tissues or within the muscle. They may be very helpful in cases without significant skin changes in planning incisions. MRI has the advantage of not requiring the administration of intravenous contrast material which may be toxic to the kidneys. This is especially helpful in patients who already have compromised renal function. However, systemically compromised patients are often logistically poor candidates for MRI scanning. In most cases, diagnostic imaging is only confirmatory, as patients with nonspecific findings on evaluation, such as edema, may still harbor the disease. Failure to improve with appropriate antibiotics, development of systemic toxicity, or profound elevation of the WBC should markedly raise the index of suspicion.

PATHOPHYSIOLOGY

The ability of an organism to cause infection is dependent on the virility of the organism and the resistance of the host. This disease is unique in that it affects both the compromised and the uncompromised host. Multiple reviews identify multiple risk factors associated with increased susceptibility; however, exceptionally virulent bacteria such as GAS are able to affect otherwise uncompromised hosts. These bacteria produce exotoxins that activate cytokines, leading to a robust systemic response. At the cellular level, the toxins and enzymes (hyaluronidases and lipases) facilitate the spread of bacteria along fascial planes and through the subcutaneous tissue. Necrosis of the superficial fascia and fat often produce a thin, watery, foul-smelling fluid (dishwater pus). The skin necrosis that may accompany this infection results when thrombosis of the skin’s nutrient vessels occurs. Microscopic findings are usually severe subcutaneous fat necrosis, severe inflammation of the dermis and subcutaneous fat, vasculitis, endarteritis, and local hemorrhage. The fascia may be edematous and suppurative, and thrombosis of vessels may be seen. Myonecrosis may also be seen in advanced cases.

SURGICAL TREATMENT

Necrotizing fasciitis is a surgical emergency. The mainstay of treatment is surgical debridement. These procedures can be quite deforming, requiring the removal of large amounts of skin, subcutaneous fat, fascia, and possibly muscle or bone. Explorations on the extremities are usually begun by making generous vertical incisions. When involvement is diffuse, fasciotomy incisions on the extremities are often a useful starting place. The dissection must extend down to the level of the deep fascia. The muscle should also be inspected to confirm its viability (Figure 2). Formal fasciotomies may be necessary in cases with very intense edema in order to prevent myonecrosis (Figure 3).

Figure 2 Lower extremity fasciotomy.

Figure 3 Upper extremity fasciotomy.

The integrity of the tissue plane between the subcutaneous fat or superficial fascia and the deep fascia is tested with either a finger or clamp (Figure 4). Lack of resistance to this probing is the hallmark of the diagnosis in early cases. “Dishwater pus” may be encountered as this plane is opened. In more advanced cases, frankly necrotic or purulent material is encountered. Cultures for stat Gram stain and aerobic and anaerobic cultures should be obtained. If the patient is immunosuppressed, cultures for Mycobacterium and fungus should also be sent. It is imperative to widely open all affected tissue planes and debride all obviously devitalized tissue (Figure 5).

Figure 4 Loss of tissue plane integrity.

Figure 5 Thorough debridement.

When the presentation is more focal, incisions can be placed over the area of maximal skin abnormality and the incision extended as abnormalities of the deeper tissue are encountered. A colostomy may be helpful in cases with extensive perianal involvement to prevent ongoing stool contamination. Surgical feeding tube placement should be considered in critically ill patients or in patients with large surface area wounds that are likely to remain open for some time.

Plans should be made at the end of the case for return to the operating room for re-evaluation of the wounds within 48 hours. Adequate evaluation of these deep and often painful wounds is not possible at the bedside. A variety of wound dressings can be applied. Negative pressure wound therapy (NPWT) is optimally suited for this purpose. It allows removal of exudate, which may further decrease bacterial counts. It prevents maceration of the surrounding tissue and keeps the patient and their bed linens dry. It is often helpful to be able to quantify the fluid losses that are occurring. Replacement of these losses may be necessary. The skin surrounding the wound can be evaluated for advancing cellulitis or edema. The character of the fluid can also be assessed.

It is imperative if this type of wound care is to be used that hemostasis is meticulous and coagulopathy corrected. Parameters must be given to the nursing staff regarding volume and character of the fluid loss that is acceptable. When this type of dressing is not available or prudent, the wounds may be packed with Kerlix (Kendall Kerlix AMD) or gauze impregnated with antimicrobial material. Although some of these materials may be cytotoxic, the antimicrobial properties may outweigh the negative effect of the cytotoxicity on normal tissues. Once the infection is controlled, non-cytotoxic products should be used. Silver ion–based products are a good choice.

BACTERIOLOGY

Necrotizing fasciitis is usually divided into two categories. Type I is a polymicrobial infection and is the most common variety. Typically this infection is seen in patients with comorbidities. Gram-negative enteric bacteria are seen in combination with Gram positives and anaerobes. Type II is GAS either alone or in combination with S. aureus. This type takes a more virulent course and occurs in younger, healthier patients. Clostridial infections classically produce air in the soft tissues, although the polymicrobial type I infections may also produce GAS. Vibrio vulnificus and Aeromonas hydrophilia should be suspected when the patient has been exposed to shellfish or freshwater.

PHARMACOLOGIC THERAPY

Initial treatment of the patient in shock should be aimed at resuscitation. Fluids and blood products are given as needed to replace deficits. Coagulation abnormalities should be corrected. It must be stressed that resuscitation is begun, but all abnormalities will not and need not be fully corrected before proceeding to surgery. Resuscitation must continue throughout the preoperative, operative, and postoperative phases. Many abnormalities will not fully correct until there is adequate source control. Pressors and steroids may be necessary in severe cases. When GAS is involved, intravenous immunoglobulin (IVIG) may also be given. Broad spectrum antibiotic therapy is initiated to cover the most likely causative organisms. Extended spectrum penicillins are a good first-line choice. Clindamycin should be added in cases that may involve GAS. Methicillin resistance is emerging in the community, and this must be considered in choosing antibiotics. Vancomycin or daptomycin should be considered when resistance is suspected or in cases where the patient is severely compromised. Patients with penicillin allergies can be treated with fluoroquinolones in combination with Gram-negative and anaerobic therapy or carbapenems.

HYPERBARIC OXYGEN

Hyperbaric oxygen (HBO) is an adjunct to resuscitation, surgical debridement, and broad spectrum antibiotics. A variety of salutary affects have been attributed to HBO therapy (Table 4). There are no prospective randomized studies to scientifically validate the efficacy of hyperbaric oxygen therapy. There are a number of retrospective studies that seem to support its use in severe necrotizing infections. Several studies demonstrated decrease mortality in patients treated with HBO compared with historic controls. Other studies demonstrated improved preservation of tissue as evidenced by a decrease in the number of debridements to achieve control of the infection. Some studies, however, have questioned the efficacy of HBO. These studies showed no statistically significant difference in mortality between patients treated with HBO and those who received only surgical debridement. HBO therapy is not uniformly available throughout the country, so it is not an option for every patient who presents with this problem. When available, given the relatively high mortality and morbidity, use of this modality as an adjunct makes sense.

Table 4 Beneficial Effects of HBO

MORTALITY, MORBIDITY, AND COMPLICATIONS MANAGEMENT

The morbidity following the treatment of severe necrotizing soft tissue infections can be severe. Most of the morbidity results from the tissue destruction brought about by the infection. The extent of morbidity depends on the area involved and the extent of the necessary debridement. During debridement, iatrogenic injury to nerves and blood supply can compound dysfunction. This is most common in the management of extremity infections. Tissues may be distorted by the inflammation and necrosis or scarred by prior surgery, making the identification of vital structures a challenge. It is vitally important to be familiar with the anatomy of the area. Patients may be left with significant deficits in function solely related to the magnitude of the surgical debridement. Amputation rates from 17%–33% have been documented in patients with extremity severe soft tissue infections.

Patients with abdominal sites of infection, who require debridement of their abdominal wall, are subject to the development of enterocutaneous fistulae. Management of the output of the fistula and providing for adequate nutrition are the primary management issues in the early management of this problem.

Mortality rates as high as 76% have been recorded, although contemporary studies report overall mortality in the range of 20%. Multiple factors affect mortality. Clinical presentation and speed to surgery appear to be the two most important determinants. Patients who suffer delays in obtaining surgical treatment had higher mortalities. Patients who present with organ failure or increased serum lactates also have higher mortalities. Comorbidities such as diabetes mellitus, renal failure, and advanced age, and the need for large surface area debridements have also been noted to increase mortality.

CONCLUSIONS

NSTI can occur under a variety of clinical conditions. It should be considered in postsurgical, post-traumatic wounds as well as in wounds from insect or animal bites. Differentiation from superficial infection is mandatory to assure appropriate surgical therapy is performed. Patients who fail to respond to appropriate medical therapy or who present with evidence of shock or organ dysfunction often harbor deeper infections. Patients with leukocytosis, hyponatremia, hyperglycemia, elevated creatinine, C-reactive protein, or CPK on laboratory evaluation should elicit an aggressive evaluation. This may include radiographic workup or surgical exploration. Progression of physical findings, including worsening edema, blistering, and crepitans or skin necrosis, mandates surgical exploration. Delays in treatment result in increased mortality and morbidity.