Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

13. Skin & Soft-Tissue Infections

Mark P. Wilhelm MD, FACP

Randall S. Edson MD, FACP

General Considerations

Skin and soft-tissue infections range in severity from self-limited localized inflammation to rapidly progressive, life- and limb-threatening necrosis with severe systemic toxicity. The clinician must be alert to clinical symptoms and signs that help to distinguish between an inflammatory process that is likely to respond to antimicrobial therapy alone and one that is rapidly progressing and requires prompt surgical intervention. We address the following clinical entities: primary pyodermas (localized bacterial infections involving the skin and/or its appendages), necrotizing soft-tissue infections, infections associated with human or animal bites, and diabetic foot infections.

When evaluating a patient with soft-tissue infection, it is important to define the host (eg, immune status, integrity of integument, etc), obtain a detailed patient history, and examine the patient with careful attention to local features. For example, a patient with impaired cell-mediated immunity, due either to exogenous factors (eg, corticosteroid therapy) or an underlying immunosuppressive disease process (eg, late-stage HIV infection or hematologic malignancy), may be susceptible to infection from opportunistic microorganisms (eg, Cryptococcus neoformans, nontuberculous mycobacteria, and filamentous fungi), causing cellulitis which may be difficult to distinguish from typical staphylococcal or streptococcal cellulitis.

Historical features to be carefully investigated include symptoms of systemic toxicity (eg, fever, chills, or prostration), the rate of progression of the inflammatory process, the presence or absence of significant pain in the involved area, recent environmental exposures, the occurrence of a precipitating event (eg, a puncture injury or animal bite), and the presence of an associated underlying disease. Necrotizing infections occur most commonly in association with advanced age or underlying comorbidity (eg, peripheral vascular disease, diabetes mellitus, alcoholism, malignancy, organ failure, or immunosuppressive therapy).

The presence or absence of fever and other signs of systemic toxicity (eg, hypotension, confusion, or oliguria) should be noted during physical examination. A careful examination of the involved area should include an assessment of the presence of erythema, induration, lymphangitis, crepitus, tenderness, duskiness (evidence of ischemia), and bullae, as well as the presence and characteristics of any drainage. The presence of gas in soft tissues is not a pathognomonic sign for the presence of anaerobic bacteria; more common causes of gas include mechanical trauma and infection with aerobic/facultative gram-negative bacilli such as Escherichia coli. Because the disease may progress rapidly, frequent reassessment and monitoring are essential.

Soft-tissue infection syndromes are best understood and defined by considering the specific anatomic structures involved and the microbial etiology. Figure 13-1 provides an overview of the anatomy of soft tissue that should help facilitate understanding of specific clinical syndromes.

THE PYODERMAS

IMPETIGO

Essentials of Diagnosis

  • A vesiculopustular or crusted superficial skin infection usually caused by Streptococcus pyogenesand/or Staphylococcus aureus.
  • Absence of pain and constitutional symptoms
  • Healing occurs without scarring.

General Considerations

Impetigo is generally considered a disease of early childhood, although it is occasionally seen in the elderly and in immunocompromised patients of all ages. Impetigo is more common in warmer climates and is typically caused by group A streptococci (GAS) (ie, S pyogenes). S aureus may also cause impetigo, occasionally in combination with GAS (Box 13-1). A bullous form of impetigo, which occurs in newborn and very young children, is caused by S aureus of phage group II.

Clinical Findings

Impetigo is a very superficial bacterial skin infection that begins with the formation of vesicles and

P.178


pustules in the epidermis beneath the stratum corneum. These lesions eventually rupture and release a honey-colored liquid, which forms a yellowish-brown crust. Impetigo typically develops on the face or on the extremities in areas that have sustained minor trauma. Pruritus is common—scratching of lesions can result in the spread of infection to previously uninvolved sites. The infection remains superficial and generally does not result in ulceration or scarring. Fever or other constitutional symptoms are absent or minimal.

 

Figure 13-1. Anatomic and clinical classification of soft-tissue infections. (Reproduced with permission from American College of Chest Physicians.)

Differential Diagnosis

Clinical entities that may be confused with impetigo include contact dermatitis, herpes simplex virus infection, and insect bites.

Complications

Occasionally, infections caused by nephritogenic strains of GAS can result in poststreptococcal glomerulonephritis. Mentioned in treatment section.

Treatment

Although impetigo may resolve spontaneously without anti-infective therapy, treatment is generally recommended for more rapid resolution of established lesions, deterring the formation of new lesions, preventing evolution to cellulitis, and possibly preventing the development of post-streptococcal glomerulonephritis, which occasionally follows infection caused by nephritogenic GAS strains (Box 13-2). Treatment options include a 10-day course of oral dicloxacillin sodium, a first-generation cephalosporin (eg, cephalexin), clindamycin, or topical mupirocin. It has not been established conclusively that antibacterial therapy is effective in reducing the incidence of nephritis.

BOX 13-1 Microbiology of Nonnecrotizing Soft-Tissue Infections

Syndrome

More Frequent

Less Frequent

Impetigo

S pyogenes, S aureus

 

Erysipelas

S pyogenes

S aureus

Ecthyma

S aureus, S pyogenes

P aeruginosa

Cellulitis

S pyogenes, S aureus

H influenzae, P multocida, Enterobacteriaceae, Aeromonas spp.

Cutaneous abscess

S aureus

Furuncle

S aureus

Carbuncle

S aureus

Folliculitis

S aureus

P aeruginosa

ERYSIPELAS

Essentials of Diagnosis

  • Edematous, red, indurated, spreading lesion.
  • Sharply demarcated, advancing, elevated margin.
  • Occurs most commonly on the face.
  • Pain, fever, and systemic toxicity are common.

General Considerations

Erysipelas is distinguished from cellulitis in that it involves the more superficial layers of the skin and cutaneous lymphatics and is more sharply demarcated; cellulitis tends to extend more deeply into subcutaneous tissues. It most commonly occurs on the face or extremities and is almost always caused by GAS. Rarely, other β-hemolytic streptococci or even S aureus may cause erysipelas. Organisms generally gain access through a break in the skin. Erysipelas tends to recur in an area of previous infection, particularly in patients with lymphedema or venous insufficiency. Facial erysipelas occasionally occurs after a streptococcal upper respiratory tract infection.

Clinical Findings

This lesion typically begins as a red spot, often at the nasolabial groove. Inflammation spreads, resulting in a tender, warm, glistening, red, edematous, and indurated area of skin. Vesicles or bullae are sometimes encountered on the surface, and there may be oozing of serous fluid. There is typically a distinct demarcation between involved and normal skin, and the area of inflammation is raised above the level of the surrounding skin. Desquamation of involved skin often occurs several days after the onset of symptoms. Skin necrosis does not occur, and healing is complete without scar formation. Associated symptoms include pain, malaise, fever, and chills. Occasionally, marked systemic toxicity is encountered.

Differential Diagnosis

The differential diagnosis of erysipelas includes cellulitis, contact dermatitis, thermal injury, and noninfectious inflammatory lesions such as the malar rash of systemic lupus erythematosus.

Treatment

In most cases of erysipelas, therapy is initiated with a parenteral agent active against β-hemolytic streptococci such as penicillin G or cefazolin (see Box 13-2). After clinical improvement is documented, therapy may be switched to an oral agent (eg, penicillin V or cephalexin). Parenteral therapy may not be necessary in mild cases with minimal systemic toxicity. Hot packs applied locally and aspirin are generally administered for symptomatic relief.

Prognosis

Skin necrosis does not occur in cases of erysipelas, and healing is generally complete without scar formation. However, involvement of superficial lymphatics may result in recurrence of erysipelas in the same area.

ECTHYMA

Essentials of Diagnosis

  • Punched-out ulcers appearing beneath adherent crusts.
  • Typically occur on lower extremities.

General Considerations

Ecthyma represents a deeper form of impetigo that begins as a vesicle and progresses to a punched-out ulcer that is surrounded by a violaceous border and covered by an adherent crust. It is most often caused by GAS, which either produce de novo lesions or infect preexisting skin lesions such as insect bites, eczema, or excoriations. Lesions with a similar clinical appearance may be encountered with bacteremia caused by Pseudomonas aeruginosa (ecthyma gangrenosum).

BOX 13-2 Empiric Therapy of Nonnecrotizing Soft-Tissue Infections

Syndrome

Treatment1

Penicillin Allergic

Impetigo

· Dicloxacillin, 250–500 mg four times daily, OR cephalexin, 250–500 mg four times daily, OR topical mupirocin

· Clindamycin, 150–300 mg four times daily OR erythromycin, 250–500 mg four times daily, or topical mupirocin

Erysipelas

· Parenteral: nafcillin, 2 g every 4–6 h, OR cefazolin, 1 g every 8h

· Oral: dicloxacillin, 500 mg four times daily OR cephalexin, 500 mg four times daily

· Parenteral: clindamycin, 600–900 mg every 8 h, OR vancomycin, 15 mg/kg every 12 h

· Oral:clindamycin, 300 mg q.i.d.

Ecthyma

· Dicloxacillin, 500 mg every 6 h, OR cephalexin, 500 mg every 6 h

· For ecthyma gangrenosum caused by P aeruginosa: piperacillin 3–4 g IV every 4–6 h + gentamicin or tobramycin, 1.5 mg/kg every 8 h OR ceftazidime, 1–2 gm IV every 8 h +/- gentamicin or tobramycin

· Clindamycin, 150–300 mg four times daily

· Ciprofloxacin, 400 mg IV or 750 mg orally every 12 h

Cellulitis

· Parenteral: nafcillin, 1–2 g every 4–6 h, OR cefazolin, 1 g every 8 h

· Oral: dicloxacillin, 500 mg four times daily OR cephalexin, 500 mg four times daily

· Parenteral: clindamycin, 600–900 mg every 8 h, OR vancomycin, 15 mg/kg every 12h

· Oral: clindamycin, 150–300 mg four times daily

Cutaneous abscess

· Parenteral: nafcillin, 1–2 g every 4–6h, OR cefazolin, 1 g every 8 h

· Oral: dicloxacillin, 250–500 mgfour times daily OR cephalexin, 250–500 mg four times daily

· Parenteral: clindamycin, 600–900 mg every 8 h, OR vancomycin, 15 mg/kg every 12 h

· Oral: clindamycin, 150–300 mg four times daily

Furuncle

· Antimicrobial therapy generally not indicated; if associated cellulitis: dicloxacillin, 250–500 mg four times daily OR cephalexin, 250–500 mg four times daily

· Clindamycin, 150–300 mgfour times daily

Carbuncle

· Parenteral: nafcillin, 1–2 g every 4–6 h OR cefazolin, 1 g every 8 h

· Oral: dicloxacillin, 500 mg dour times daily OR cephalexin, 500 mg four times daily

· IV: clindamycin, 600–900 mg every 8 h, OR vancomycin, 15 mg/kg every 12 h

· Oral:clindamycin, 300 mg four times daily

Folliculitis

· Antimicrobial therapy generally not indicated

1Suggested dosages are for patients with normal renal function; quinolone antibacterial agents should be avoided in children and adolescents < 18 years old; pediatric dosages can be found in the Pocket Book of Pediatric Antimicrobial Therapy, 13th ed. Williams & Wilkins, 1998.

Clinical Findings

Ecthyma typically occurs as a single erythematous ulceration or multiple erythematous ulcerations with overlying crusts on the lower extremities, especially in areas of minor trauma. Because of the deeper level of infection, ecthyma—unlike impetigo—often heals with scarring.

Treatment

The approach to treatment of ecthyma is the same as for impetigo. Beyond removal of crusts and debris with warm compresses, surgery is generally not indicated. Ecthyma caused by P aeruginosa requires parenteral antipseudomonal therapy and occasionally débridement (see Box 13-2).

CELLULITIS

Essentials of Diagnosis

  • Diffuse spreading infection of skin and subcutaneous tissue.
  • Inflammatory lesion is hot, red, with diffuse or vague margins.
  • Systemic toxicity is variable.

General Considerations

Cellulitis is a superficial infection of skin and subcutaneous tissues characterized by erythema, induration, and tenderness. Local trauma or underlying skin lesions are common predisposing conditions. Because inflammation from an episode of cellulitis, erysipelas, or lymphangitis can result in obstruction of lymphatic drainage, initial episodes are associated in many cases with an increased predisposition to develop recurrent infections involving the same area. Most cases are caused by either S pyogenes or S aureus. Mixed streptococcal and staphylococcal infection may also occur. Less common bacterial etiologies include groups B, C, and G streptococci, Haemophilus influenzae (in children), Streptococcus pneumoniae, Pasteurella multocida (cat or dog bites), enteric bacilli (Enterobacteriaceae), anaerobic bacteria, Legionella spp., P aeruginosa, Helicobacter cinaedi (immunocompromised patients), Aeromonas hydrophila (freshwater exposure), and Vibrio vulnificus (seawater exposure). Erysipelothrix rhusiopathiae is the etiologic agent of erysipeloid, which is a violaceous cellulitis of the hands occurring in persons handling raw fish, meat, or poultry. Nonbacterial causes of cellulitis, such as Cryptococcus neoformans, filamentous fungi, and nontuberculous mycobacteria, should be considered in unusual cases, particularly with immunocompromised patients.

Clinical Findings

  1. Signs and Symptoms.Cellulitis typically presents with erythema, warmth, swelling, and local pain and tenderness. In contrast to erysipelas, the margins of the inflammatory erythematous lesion are neither elevated nor sharply demarcated from surrounding uninvolved tissue. The involved area is often quite extensive and may progress rapidly, particularly in patients with chronic dependent edema. Lymphangitis with regional lymphadenopathy is common. Although it is presumed that cellulitis often begins at the site of a break in the skin, this is often not clinically apparent. Systemic features of cellulitis vary considerably, ranging from the complete absence of systemic illness to severe systemic toxicity. Fever, chills, and malaise accompany most cases of significant bacterial cellulitis.
  2. Laboratory Findings.Blood cultures should be obtained in most cases of cellulitis, before the initiation of empiric antimicrobial therapy. Although the culturing of a punch biopsy specimen or leading-edge aspirate has often been advocated, positive cultures occur in only ~20% of cases. This diagnostic approach is usually not necessary and is in practice rarely pursued in cases of uncomplicated bacterial cellulitis. However, material for culture should be obtained by aspiration, or biopsy should be considered in unusual cases, particularly in cases of necrotizing infection and in immunocompromised patients, who may develop soft-tissue infections that are caused by unusual pathogens.
  3. Imaging.Most cases of simple bacterial cellulitis do not require radiologic investigations. Plain radiographs may disclose the presence of foreign bodies, adjacent bony involvement, or gas in soft tissues.

Differential Diagnosis

The differential diagnosis of cellulitis includes a wide variety of infectious and noninfectious inflammatory lesions, including erysipelas, erysipeloid, thermal injury, infiltrative malignancies, angioedema, neutrophilic dermatosis (Sweet's syndrome), erythema chronicum migrans, and cutaneous herpes zoster.

Complications

Although many instances of limited cellulitis resolve without treatment, cellulitis can cause serious disease by spreading rapidly via lymph vessels and the bloodstream. Patients who have undergone saphenous venectomy for myocardial revascularization may develop recurrent acute cellulitis in the involved limb, often with associated lymphangitis. These episodes are generally caused by non-group A β-hemolytic streptococci and commonly occur in association with tinea pedis, which may serve as a nidus for streptococcal colonization. Episodes tend to recur over many months or even years. Treatment of the dermatophytic fungal infection may abolish recurrent cellulitis episodes. Recurrent streptococcal cellulitis also occurs in patients with lymphedema of a limb, which may be caused by mastectomy, radiation therapy, radical pelvic surgery, or neoplastic involvement of lymph nodes. Although most cases of cellulitis resolve without suppurative complications, localized inflammation may occasionally evolve into a subcutaneous abscess that requires drainage.

Treatment

Uncomplicated bacterial cellulitis is most commonly caused by β-hemolytic streptococci or S aureus. Because the clinical features of streptococcal, staphylococcal, or combined infections are usually similar, in most cases therapy is directed against both streptococci and staphylococci without confirmation of the etiology. If the infection is mild, an oral agent such as dicloxacillin or a first-generation cephalosporin (eg, cephalexin) may be selected (see Box 13-2). Either a semisynthetic penicillin (eg, nafcillin or oxacillin) or a first-generation cephalosporin (eg, cefazolin) would be an appropriate first-line parenteral agent for mild cellulitis of undetermined etiology. Penicillin remains the drug of choice for streptococcal cellulitis, such as with recurrent cellulitis in a limb after saphenous venectomy.

Prognosis

The prognosis of most cases of simple bacterial cellulitis is good with appropriate antimicrobial therapy. Scarring is generally not encountered, and suppurative complications occur in a minority of cases. Episodes of cellulitis may heal with the development of lymphedema, thereby potentially predisposing the patient to recurrent episodes in the same location.

Prevention

Treatment of tinea and management of edema in involved limbs with appropriate mechanical measures such as support hose may lessen the risk for the development of bacterial cellulitis.

CUTANEOUS ABSCESSES

Essentials of Diagnosis

  • A fluctuant, erythematous, tender, cutaneous nodule.
  • Associated purulent drainage may occur.
  • Features of systemic illness are variably present.

General Considerations

Cutaneous abscesses most commonly evolve by local extension of a primary epidermal/dermal infection. Although localized suppuration occurs, host defenses prevent systemic spread of the infection. Thus, cutaneous abscesses tend to be superficial, single, and well localized, and are not associated with systemic toxicity. A subcutaneous abscess may also arise through trauma, such as from puncture injuries. Abscesses may occur by hematogenous seeding of cutaneous/subcutaneous tissue, as is occasionally seen in the setting of S aureus bacteremia. Cutaneous abscesses may occur in any location, although they most commonly involve the head, neck, extremities, and perineal region. Cutaneous abscesses usually contain organisms that reflect the flora of the overlying skin or adjacent mucous membrane. Abscesses on the trunk or extremities are commonly caused by S aureus or streptococci.

Clinical Findings

Cutaneous abscesses are recognized clinically as tender, painful, erythematous nodules that become fluctuant. There may be evidence of surrounding inflammation or an overlying pustule.

Complications

Complications of cutaneous abscesses include bacteremia and spread of infection into adjacent structures, including bone or joints.

Treatment

Most cutaneous abscesses require incision and drainage when demonstrable fluctuance is present. If only a tender nodule is encountered, needle aspiration may be performed, followed by incision and drainage if pus is recovered. Because of the potential for extension to the cavernous sinus, lesions on the nose or lips should generally not be incised or otherwise manipulated. If the lesion is effectively drained surgically, antibiotic therapy may not be necessary. Antibiotic therapy is generally reserved for high-risk patients with impaired host defenses or for patients in whom there is evidence of bloodstream invasion or extension of infection to adjacent tissues (see Box 13-2). Because drainage of subcutaneous abscesses may cause transient bacteremia, antibiotic prophylaxis should be given for patients with underlying cardiac valvular disease. Empiric adjunctive antibiotic therapy should be based on the most likely bacterial pathogen(s). In most cases, a first-generation oral cephalosporin or an antistaphylococcal penicillin would be an appropriate agent. Definitive treatment can subsequently be selected based on culture and susceptibility data.

FURUNCLES AND CARBUNCLES

Clinical Findings

Furuncles present as tender, firm, erythematous nodules that become fluctuant. They develop from folliculitis, spreading to the subcutaneous layers of the skin. Furuncles occur in moist areas of skin that contain hair follicles and are subject to friction (eg, neck, axillae, buttocks, and face). An inflammatory nodule becomes fluctuant with subsequent spontaneous drainage of pus. Predisposing conditions include diabetes mellitus, corticosteroid therapy, and use of injected drugs.

A carbuncle is a more extensive, multiloculated subcutaneous lesion that occurs most commonly at the nape of the neck. It often drains along hair follicles from deep, septate pockets of suppuration; multiple sinus tracts are frequently present. Carbuncles tend to occur in areas covered by thick inelastic subcutaneous tissue such as the nape of the neck, back, or thighs; they are generally quite painful.

Both furuncles and carbuncles are almost always caused by S aureus. Although systemic manifestations are not encountered with furuncles, fever and other systemic symptoms are frequently seen with carbuncles. Patients with recurrent furunculosis should be evaluated for the possibility of nasal carriage of S aureus.

Complications

Manipulation of furuncles on the upper lip or near the nasolabial groove should be avoided, because it may result in cavernous sinus thrombosis. Staphylococcal bacteremia may be encountered with large, inflamed lesions, possibly resulting in metastatic abscesses.

Treatment

For minor furuncles, moist heat should provide adequate therapy. Topical or systemic anti-infective therapy is generally not indicated. Larger furuncles and carbuncles require incision and drainage as well as oral or, occasionally, parenteral antistaphylococcal therapy.

FOLLICULITIS

Clinical Findings

Folliculitis is a bacterial infection that involves the ostium of a hair follicle, typically on the face, buttocks, or the extensor surface of an extremity. The lesions consist of small, tender erythematous papules or pustules that eventually drain, become crusted, and spontaneously heal. Lesions in different stages of evolution are often present simultaneously. Most cases of folliculitis are caused by S aureus, although folliculitis caused by P aeruginosa may be encountered in the setting of contaminated swimming pools or hot tubs. Healing occurs spontaneously in most cases, either by drainage or regression. Scarring is distinctly uncommon.

Treatment

Anti-infective therapy is generally not indicated. Local heat may provide symptomatic benefit.

NECROTIZING SOFT-TISSUE INFECTIONS

Essentials of Diagnosis

  • Usually rapidly progressive infections with evidence of soft-tissue necrosis.
  • Marked systemic toxicity generally but not invariably present.
  • Multisystem organ failure may occur.
  • Involved area generally painful.
  • Variable microbiology—monomicrobial (eg, GAS, Clostridiumspp.) vs polymicrobial.

General Considerations

Necrotizing soft-tissue infections are characterized by rapidly progressive inflammation and necrosis variably involving skin, subcutaneous fat, fascia, and occasionally muscle. Many classification schemes have been proposed for necrotizing soft-tissue infections, but they are often inconsistent and imprecise. In many cases, a variety of terms have been given to closely related or essentially identical processes. Furthermore, the classifications have been difficult to apply clinically and have resulted in considerable confusion in clinical practice. In approaching this group of infections, emphasis should be placed on differentiating necrotizing infections, which require prompt surgical intervention, from non-necrotizing infections, which usually do not.

Early clinical signs of a necrotizing infection include the presence of bullae, edema that extends beyond the area of erythema, focal cutaneous ecchymosis/ischemia, crepitus, cutaneous anesthesia, and the absence of lymphangitis. Early in the course of a necrotizing infection, patients complain of severe pain, usually out of proportion to the physical findings. Although skin changes are usually present, cutaneous evidence of necrotizing fasciitis may be absent. The most clinically important distinctions to be made in defining necrotizing soft-tissue infection syndromes are the tissues/structures involved and the microbial etiology.

Most necrotizing soft-tissue infections are polymicrobial, although there are two important exceptions: clostridial myonecrosis and type-2 necrotizing fasciitis caused by invasive GAS. All necrotizing soft-tissue infections should be cultured and require prompt surgical débridement and parenteral antimicrobial therapy (Boxes 13-3 and 13-4).

Ultrasonography is helpful in evaluating the possibility of complicating abscess formation and for providing imaging capability at the bedside in emergency situations. Although computed tomography scans provide considerable information about the extent of infection, magnetic resonance imaging provides the greatest resolution and level of detail in the definition of complex soft-tissue infection syndromes. In cases of suspected deep and/or necrotizing infections that are not clinically obvious, magnetic resonance imaging scans may provide substantial diagnostic benefit. However, pursuing imaging studies should not delay life-saving surgical intervention, which is also the most definitive mode of diagnosis. Detection of a significantly elevated serum creatine kinase level suggests involvement of muscle in the disease process.

The key to a successful outcome in the treatment of necrotizing soft-tissue infections is early diagnosis and treatment. Early findings of necrotizing infections may appear similar to nonoperative cellulitis; therefore, correct early diagnosis requires a high index of suspicion and an awareness of specific clinical findings that suggest a necrotizing infection.

BOX 13-3 Microbiology of Necrotizing Soft-Tissue Infections

Syndrome

Usual Microbiology

Clostridial myonecrosis (gas gangrene)

· Clostridium spp. (C perfringens, occasionally C septicum, or others)

Type-1 (polymicrobial) necrotizing fasciitis

· Mixedaerobes and anaerobes

Type-2 (streptococcal) necrotizing fasciitis

· S pyogenes

Progressive bacterial synergistic gangrene

· Microaerophilic streptococci Plus S aureus (or occasionally Proteus spp.)

Clostridial anaerobic cellulitis

· C perfringens

Nonclostridial anaerobic cellutitis

· Mixed aerobes and anaerobes

Classification problems notwithstanding, several relatively well-defined necrotizing soft-tissue infection syndromes regularly encountered in the medical literature are discussed in the following sections.

CLOSTRIDIAL MYONECROSIS (GAS GANGRENE)

General Considerations

Clostridial myonecrosis (gas gangrene), usually caused by Clostridium perfringens, is an extremely serious, rapidly progressive infection that poses imminent risk to limb and life. It typically occurs in settings characterized by the presence of contaminated, devitalized tissue. Predisposing conditions include traumatic injuries such as compound fractures, penetrating wounds (eg, combat-induced wounds), surgical wounds after enteric surgery, and limb injuries in the setting of advanced arterial insufficiency.

Clinical Findings

There is rapid destruction of muscle and usually severe systemic toxicity. Prompt débridement of all nonviable tissue, often leading to amputation, is essential for cure. At surgery, involved muscle is typically pale and edematous and does not contract when probed.

A variant syndrome, referred to as spontaneous nontraumatic gas gangrene, occurs in the absence of trauma in patients with underlying diseases such as colon cancer, leukemia, or diabetes mellitus. It is commonly caused by Clostridium septicum and is thought to occur via hematogenous seeding.

The onset of gas gangrene is sudden, with severe pain, hypotension, and systemic toxicity. The affected limb becomes edematous; the surrounding skin is pale; a blood-tinged, serous discharge may be noted; and the surrounding tissue finally becomes dusky with fluid-filled bullae. In addition, gas may be palpable in the tissues.

Complications

Severe tissue destruction is generally encountered with gas gangrene, which may lead to loss of limb or death.

Treatment

When Clostridium spp. have been demonstrated or are highly suspected, high-dose penicillin G is generally considered the drug of choice (see Box 13-4). Although some studies have shown increasing resistance of clostridia to penicillin, almost all strains of C perfringens remain susceptible. Metronidazole, imipenem, clindamycin, and ampicillin/sulbactam or piperacillin/tazobactam are possible alternatives. It should be noted that clindamycin is relatively inactive in vitro against some strains of Clostridia spp. The combination of penicillin and clindamycin is often used in the setting of clostridial myonecrosis, largely based on experimental evidence in animals.

Although it is reasonable to use adjunctive hyperbaric oxygen therapy when available, under no circumstances should débridement be delayed to facilitate transport to a facility with hyperbaric oxygen facilities. Prompt surgical débridement should be performed, with removal of all devitalized tissue.

Prognosis

Prompt recognition and adequate débridement of devitalized tissues are essential to minimize tissue loss. More proximal amputation may sometimes be necessary if initial débridement is inadequate.

Prevention

Meticulous care of contaminated traumatic wounds, including thorough débridement of devitalized tissue and foreign material, is essential to lessen the likelihood of the development of gas gangrene.

BOX 13-4 Empiric Therapy of Necrotizing Soft-Tissue Infections

Syndrome

Treatment1

Penicillin Allergic

Clostridial anaerobic cellulitis

· Penicillin G, 24 million U IVevery 24 h by continuous infusion

· Metronidazole, 500 mg IV every 6 h, OR clindamycin 900 mg IV q8h

Type 1 (polymicrobial) necrotizing fasciitis

· Piperacillin/tazobactam, 3.375 g IV every 6 h; OR imipenem, 500 mg IV every 6 h; OR ceftria-xone, 1–2 g IV once daily + metro nidazole, 500 mg IV every 6 h

· Vancomycin, 15 mg/kg every 12 h + ciprofloxacin, 400 mg IV every 12 h + metronidazole, 500 mg IV every 6 h

Type 2 (streptococcal) necrotizing fasciitis

· Penicillin G, 24 million U IV every 24 h by continuous infusion + clindamycin, 900 mg IV every 8 h (+/- IVIG2)

· Clindamycin, 900 mg IV every 8 h (+/- IVIG2)

Progressive bacterial synergistic gangrene

· Piperacillin/tazobactam 3.375 g IV every 6 h

· Clindamycin, 900 mg IV every 8 h +/- ciprofloxacin, 400 mg IV every 12 h OR vancomycin, 15 mg/kg IV every 12 h +/- ciprofloxacin, 400 mg IV every 12 h

Clostridial myonecrosis (gas gangrene)

· Penicillin G, 24 million U IV every 24 h by continuous infusion (+/- clindamycin, 900 mg IV every 8 h)

· Metronidazole, 500 mg IV every 6 h

Nonclostridial anaerobic cellulitis

· Piperacillin/tazobactam, 3.375 g IV every 6 h, OR imipenem, 500 mg IV every 6 h, OR ceftriaxone, 1–2 g IV once daily + metronidazole, 500 mg IV every 6 h

· Vancomycin, 15 mg/kg every 12 h + ciprofloxacin, 400 mg IV every 12 h + metronidazole, 500 mg IV every 6 h

1Suggested dosages are for patients with normal renal function; quinolone antibacterial agents should be avoided in children or adolescents < 18 years of age; pediatric dosages can be found in the Pocket Book of Pediatric Antimicrobial Therapy, 13th ed. Williams & Wilkins, 1998.
2IVIG, Intravenous immunoglobin

 

NECROTIZING FASCIITIS

General Considerations

Necrotizing fasciitis is an infectious process that progressively destroys the subcutaneous fascia and fat with relative sparing of underlying muscle. Although it may affect any part of the body, including the abdominal wall and perineum, necrotizing fasciitis occurs most commonly on the extremities.

Clinical Findings

Early findings of necrotizing fasciitis may resemble cellulitis. However, the process spreads rapidly and is usually associated with severe pain and significant systemic toxicity. Edema may extend beyond the area of cutaneous inflammation. Infection spreads rapidly along fascial planes and through venous and lymphatic channels. Although there is often evidence of cutaneous necrosis, necrotizing fasciitis may occur with relatively intact overlying skin, particularly with an early presentation. Patchy cutaneous anesthesia, gangrene, or both may occur as a result of extensive undermining of subcutaneous tissue, which contains vascular structures and nerves. Patients generally appear “toxic,” and hypotension and multiorgan failure often develop. The diagnosis is usually readily confirmed at surgery by the finding of gray necrotic fascia without frank pus and by easy dissection and undermining of the wound. Histopathologic findings include fascial necrosis, thrombosis of small arteries and veins, and the presence of microorganisms on Gram stains.

Based on microbial etiology, necrotizing fasciitis syndromes are classified into two types. Type-1 necrotizing fasciitis is a polymicrobial infectious process in which at least one anaerobic species (usually Bacteroides or Peptostreptococcus spp., or both) is isolated in combination with one or more facultative species, such as gram-negative bacilli of the Enterobacteriaceaefamily or streptococci (but not GAS). Fournier's gangrene represents a form of polymicrobial necrotizing fasciitis involving the male genitalia, typically occurring in diabetic patients. Synergistic necrotizing cellulitis represents essentially the same process as type-1 necrotizing fasciitis, although it often involves muscle. Type-2 necrotizing fasciitis, occasionally referred to as hemolytic streptococcal gangrene, is caused by invasive GAS, which may rarely be present in combination with another organism such as S aureus. There has been a marked increase in the reported incidence of invasive GAS infection over recent years. It often begins at the site of minor trauma. Although it typically occurs in the elderly and in patients with underlying medical conditions, it has also been encountered in otherwise healthy young patients. Varicella infection has also been shown to be a risk factor for the development of invasive S pyogenes infections. Although muscle involvement can occur, soft tissue gas is not seen. This type of necrotizing fasciitis is often seen in association with the streptococcal toxic shock syndrome. The use of nonsteroidal anti-inflammatory agents may adversely affect the clinical outcome, and there is a significant risk of nosocomial or domestic transmission.

Differential Diagnosis

The differential diagnosis of necrotizing fasciitis includes cellulitis, clostridial myonecrosis, myositis, and anaerobic and other necrotizing forms of cellulitis.

Complications

Complications of necrotizing fasciitis include compartment syndromes, progressive limb necrosis leading to amputation, bacteremia, multiorgan failure, and death.

Treatment

In all instances where drainage is present, aerobic and anaerobic cultures and a Gram stain should be performed. Initial anti-infective therapy may then be based on the results of the Gram stain morphology (see Box 13-4). When only streptococci are seen on Gram stain in the setting of a necrotizing infectious process, then high-dose penicillin G should be administered. It has been suggested, from limited experimental data and anecdotal clinical experience, that clindamycin should be administered in addition to penicillin in cases of invasive infection caused by S pyogenes, because of the theoretical ability of clindamycin to interfere with streptococcal toxin production. There is also anecdotal evidence supporting the use of intravenous gammaglobulin in cases of streptococcal necrotizing fasciitis. No controlled data are available to clearly define the potential additive benefit of this costly adjunctive therapeutic modality, however.

When the Gram stain reveals several bacterial morphologies, broad-spectrum antibacterial therapy should be directed at gram-positive and gram-negative anaerobic and aerobic/facultative organisms. Polymicrobial Gram stain findings may be encountered in many of the polymicrobial syndromes described above, including type-1 necrotizing fasciitis, progressive synergistic gangrene, and nonclostridial anaerobic cellulitis. Reasonable initial therapeutic regimens, pending definitive culture and susceptibility data, include (1) a third-generation cephalosporin (eg, cefotaxime or ceftriaxone) in combination with metronidazole or clindamycin; (2) ampicillin, gentamicin, and clindamycin or metronidazole; (3) piperacillin/tazobactam monotherapy; or (4) imipenem monotherapy.

Prognosis

The prognosis of necrotizing fasciitis largely depends on early recognition, prompt institution of antimicrobial therapy, and early complete débridement of all devitalized tissue.

PROGRESSIVE BACTERIAL SYNERGISTIC GANGRENE

This soft-tissue infection syndrome, also known as Meleney's synergistic gangrene, typically results from infection at the site of an abdominal surgical incision, around an enterostomy, in association with an abdominal fistula exit site, or in association with a chronic lower-extremity ulcer. As the term synergistic implies, this infection typically has a polymicrobial etiology and most commonly involves anaerobic or microaerophilic streptococci with S aureus or occasionally facultative gram-negative bacilli such as Proteus spp.

Progressive bacterial synergistic gangrene begins as a localized area of swelling, erythema, and tenderness that becomes ulcerated and gradually enlarges. Fever is usually minimal or absent. The ulcer is characteristically encircled by gangrenous skin with surrounding violaceous skin.

ANAEROBIC CELLULITIS

Clostridial anaerobic cellulitis describes an infection, usually caused by C perfringens, that typically involves devitalized subcutaneous tissues that result from a contaminated or inadequately débrided traumatic or surgical wound. Nonclostridial anaerobic cellulitis is clinically similar to clostridial anaerobic cellulitis but is caused by non–spore-forming anaerobic bacteria (eg, Bacteroides spp., peptostreptococci, and peptococci) often in conjunction with facultative organisms such as Enterobacteriaceae, streptococci, or staphylococci. Gram stains and cultures of exudate aspirated from the lesion will typically suggest the polymicrobial nature of this process.

Gas formation is evident in skin and subcutaneous tissue on examination and radiographically, and thin, malodorous drainage may emanate from the wound. There is no appreciable involvement of deeper structures such as fascia or muscle. The onset is generally gradual, and there is usually mild local pain and systemic toxicity, allowing clinical differentiation from the more fulminant clostridial myonecrosis.

INFECTIONS ASSOCIATED WITH HUMAN OR ANIMAL BITES

Essentials of Diagnosis

  • Acute soft-tissue infection occurring at the site of a bite injury.
  • May involve deeper structures such as joint space, tenosynovium, or bone.
  • Etiology often polymicrobial—P multocidacommonly seen with dog bite or cat bite infections.

General Considerations

Human and animal bite wounds account for ~1% of emergency room visits. Half of all Americans at some time during their lives are bitten by a cat or dog. These wounds can be clinically quite deceptive, because what initially appears to be a minor wound may involve the subjacent joint space or bone, resulting in serious complications. Box 13-5 summarizes the most common causes of each type of infection.

  1. Dog Bites.Dog bites account for ~80% of animal bite wounds; 15–20% of these wounds become infected. The risk of infection is increased in the presence of associated crush or puncture injuries and involvement of the hand. Organisms generally encountered are found in the oral flora of dogs: P multocida, S aureus, streptococci, and occasionally Capnocytophaga canimorsus, Eikenella corrodens, other gram-negative bacilli, and anaerobes.
  2. Cat Bites.Cats have slender and extremely sharp teeth that typically cause a puncture-type injury with potential involvement of bone or joint. The overall rate of wound infection after cat bites is >50%, with a proportionate increase in the incidence of associated septic arthritis and osteomyelitis. P multocidais the most frequently isolated pathogen, occurring in >50% of cases. Other organisms, similar to those associated with dog bite injuries, may also be recovered.
  3. Human Bites.Human bites tend to be more serious and more prone to infection than animal bites, in part because of the typical mechanisms of injury (eg, clenched fist and occlusional injuries). Clenched-fist injuries typically involve trauma to the metacarpophalangeal joints, and thus are at high risk for complications such as deep soft-tissue infections, septic arthritis, and osteomyelitis. Potential pathogens include S aureus, H influenzae, E corrodens, and anaerobic bacteria, including strains that produce β-lactamases.

BOX 13-5 Microbiology of Bite-Associated Infections

Type of Bite

Usual Microbiology

Dog

· Streptococci, S aureus, Eikenella corrodens, Pasteurella multocida, Capnocytophaga canimorsus, anaerobes

Cat

· P multocida, streptococci, anaerobes

Human

· S aureus, E corrodens, H influenzae, anaerobes

Treatment

Wounds should be irrigated with saline and may require débridement and surgical repair depending on the severity of the injury. The risk for rabies infection should be assessed carefully and appropriate prophylaxis given, if indicated. Tetanus prophylaxis should also be addressed. If a wound is brought to clinical attention >24 h after injury or if there are already signs of infection, it should be left open. If a patient presents with an infected wound, cultures for aerobic and anaerobic bacteria should be obtained. Radiography should be pursued if an underlying fracture is suspected. In general, relatively trivial bite wounds may not require antibiotic therapy, although it may be prudent to administer a short (3- to 5-day) course of a prophylactic oral antibiotic (eg, amoxicillin/ clavulanate) in the setting of a more significant bite injury (especially for cat bite injuries) (Box 13-6). For an infected wound requiring hospitalization, ampicillin/sulbactam would be a reasonable initial empiric therapeutic choice.

DIABETIC FOOT INFECTIONS

Essentials of Diagnosis

  • Acute, subacute, or chronic soft-tissue infection of diabetic feet, often with associated ulceration.
  • Commonly occurs in the setting of associated neuropathy and arterial insufficiency.
  • Fever and other systemic symptoms may or may not be present.
  • Need to exclude underlying osteomyelitis.
  • Mild, non–limb-threatening infections usually caused by S aureusor β-hemolytic streptococci.
  • Severe limb-threatening infections usually have a polymicrobial etiology.

BOX 13-6 Empiric Therapy of Bite-Associated Infections

Type of Bite

Treatment1

Penicillin Allergic2

Dog

· Oral: amoxicillin/clavulanate, 500 mg three times daily

· Parenteral: ampicillin/sulbactam, 3 g every 6 h

· Oral: Levofloxacin 500 mg once daily OR gatifloxacin 400 mg once daily
PLUS
Clindamycin 300 mg every 6 h OR metronidazole 500 mg every 6 h

· Parenteral: levofloxacin 500 mg IV once daily OR gatifloxacin 400 mg IV once daily
PLUS
Clindamycin 900 mg IV every 8 h OR metronidazole 500 mg IV every 6 h

Cat

· Oral: amoxicillin/clavulanate, 500 mg three times daily

· Parenteral: ampicillin/sulbactam, 3 g every 6 h

Human

· Oral: amoxicillin/clavulanate, 500 mg three times daily

· Parenteral: ampicillin/sulbactam, 3 g every 6 h

1Suggested dosages are for patients with normal renal function; quinolone antibacterial agents should be avoided in children and adolescents < 18 years of age; pediatric dosages can be found in the Pocket Book of Pediatric Antimicrobial Therapy, 13th ed. Williams & Wilkins, 1998.
2No alternatives have been clearly established for penicillin allergic patients.

General Considerations

Foot infections are a serious complication of diabetes mellitus and result in more days of hospitalization than any other complication. Diabetic foot infections account for >50% of all nontraumatic amputations. Underlying pathogenic factors include sensory peripheral neuropathy, macro- and microangiopathy, and systemic factors. Diminished sensation places the patient at risk for skin trauma and subsequent ulceration.

Infections typically start with a break in the skin, followed by penetration of bacteria into the skin and subcutaneous tissue (Box 13-7). This leads initially to a localized cellulitis that may spread to deeper structures including the deep fascia, tendon, joint space, or bone. Penetration by a foreign body is often asymptomatic and may lead to deep infection with limited involvement of superficial structures. Repetitive minor trauma caused by ill-fitting shoes may also lead to skin breakdown with subsequent infection. Hyperglycemia has been shown to result in polymorphonuclear cell dysfunction, which may contribute to the development and progression of infection. Diabetic foot ulcer is not a common problem in pediatric diabetes.

  1. Mild Non–Limb-Threatening Infections.Mild non–limb-threatening infections tend to be superficial, presenting with mild cellulitis and minimal systemic toxicity. They may be associated with an ulcer that, if present, does not traverse all layers of the skin. There is no subjacent bone or joint involvement and the involved limb generally has reasonably good arterial blood supply. These infections are monomicrobial in half the cases and are generally caused by S aureusor aerobic streptococci. Gram-negative bacilli and anaerobic bacteria are infrequently isolated.
  1. Severe Limb-Threatening Infections.Limb-threatening diabetic foot infections are usually polymicrobial and involve both anaerobic and aerobic bacteria, including S aureus, β-hemolytic streptococci (often group B), Enterobacteriaceae, Clostridiumspp., and Bacteroides spp. Although coagulase-negative staphylococci, enterococci, and Corynebacterium spp. are occasionally recovered in culture and may be pathogenic, the possibility of contamination or colonization should be considered, particularly when isolated from a superficial swab.

BOX 13-7 Microbiology of Diabetic Soft-Tissue Foot Infections

Type

Usual Microbiology

Mild non–limb-threatening infections

· S aureus, beta-hemolytic streptococci

Severe limb-threatening infections

· S aureus, streptococci, enterococci, Enterobacteriaceae, anaerobes, coagulase-negative staphylococci

Clinical Findings

Limb-threatening diabetic foot infections typically occur in the setting of significant limb ischemia and often with associated gangrene. The cellulitis is more extensive, and full-thickness skin ulcers are often present. There may be infection of contiguous bone and/or joint space. When fever is present, it is often seen in association with extensive soft-tissue infection, deep abscesses, bacteremia, or hematogenously seeded metastatic infection.

Diagnostic evaluation involves detailed definition of the extent of disease and the potential for wound healing. The vascular status of the involved limb should be documented by physical examination, noninvasive laboratory studies including transcutaneous oximetry, and angiography in selected cases. The possibility of concomitant subjacent osteomyelitis should be considered in all cases. Visualization of bone or the ability to “probe to bone” in infected diabetic foot ulcers has been shown to strongly correlate with the presence of underlying osteomyelitis.

All available radiographic diagnostic modalities, including plain radiographs, computed tomography scans, and technetium and radioactive leukocyte scans, have limited sensitivity and/or specificity for the definitive diagnosis of osteomyelitis. Magnetic resonance imaging is a valuable diagnostic tool for the detection of osteomyelitis in feet of diabetic patients and may be superior to radionuclide imaging.

Complications

Complications of diabetic foot infections include persistence of infection, osteomyelitis, septic arthritis, progressive infection necessitating amputation, and systemic infection with severe toxicity.

Treatment

Selection of antimicrobial therapy (Box 13-8) depends to a large extent on the nature and severity of infection. In cases of mild non–limb-threatening cellulitis without evidence of tissue necrosis and in the absence of a foul odor, therapy may be directed at gram-positive cocci (ie, S aureus) with a first-generation cephalosporin such as cefazolin. In select cases, oral therapy with an agent such as dicloxacillin or cephalexin may be appropriate. More severe infections, particularly those with associated tissue necrosis, generally require broader-spectrum therapy. Possibilities include piperacillin/tazobactam, imipenem or meropenem, or combination therapy such as cefepime with clindamycin or metronidazole. Therapy should be guided by culture and susceptibility data if appropriate specimens are available for culture. Duration of antimicrobial therapy depends on specific clinical circumstances. Cases of mild cellulitis are generally treated for 7–10 days.

More severe soft-tissue infection may require 2–3 weeks of therapy. If osteomyelitis is present and complete surgical resection of diseased bone is not performed, a minimum of 4 weeks of parenteral therapy is usually indicated. Surgical removal of devitalized tissue and drainage of pus are important components of therapy. If osteomyelitis is present, the surgical approach should be dictated by the extent of bone involvement and the vascular status of the limb. Revascularization should be pursued in ischemic limbs to facilitate healing, if technically feasible.

Considerable controversy exists concerning the surgical approach to diabetic foot infections and the extent of débridement required for treatment of infected bone. Limited ablative surgery to remove infected bone, such as with toe amputation or ray resection, often allows for a shortened course of antibiotic therapy, a shorter hospital stay, a greater likelihood of cure, and an earlier return to normal living. In cases of severe underlying arterial occlusive disease that is not amenable to surgical repair or in the presence of significant tissue necrosis, more proximal amputation may be necessary.

Prognosis

The outcome of the treatment of diabetic foot infections is to a great extent related to the underlying vascular and neurologic status of the limb. In infections involving relatively well-perfused limbs, amputation is less likely to be necessary for ultimate cure. In general, severe infection in severely ischemic limbs requires amputation.

BOX 13-8 Empiric Therapy of Diabetic Soft-Tissue Foot Infections

Type

Treatment1

Penicillin Allergic

Mild non-limb-threatening infections

· Oral: cephalexin 500 mg four times daily; OR amoxicillin/clavulanate, 500 mg three times daily

· Parenteral: cefazolin, 1 g every 8 h, OR ampicillin/sulbactam, 1.5–3 g IV every 6 h

· Oral: clindamycin, 300 mg four times daily

· Parenteral: clindamycin, 600–900 mg every 8 h, OR vancomycin, 15 mg/kg every 12 h

Severe limb-threatening infections

· Piperacillin/tazobactam, 3.375–4.5 g IV every 6 h, OR cefepime, 1–2 g IV every 12 h + metronidazole, 500 mg IV every 6 h, OR meropenem. 1 g IV every 8 h

· Clindamycin, 900 mg IV every 8 h + ciprofloxacin, 400 mg IV every 12 h, OR vancomycin, 15 mg/kg IV every 12 h + ciprofloxacin, 400 mg IV every 12 h + metronidazole, 500 mg IV every 6 h

1Suggested dosages are for patients with normal renal function; quinolone antibacterial agents should be avoided in children and adolescents < 18 years of age; pediatric dosages can be found in the Pocket Book of Pediatric Antimicrobial Therapy, 13th ed. Williams & Wilkins, 1998.

Prevention

Preventive measures that may lessen the incidence of diabetic foot infections include meticulous foot care, the use of properly fitting footwear, early treatment of mild infections, and optimizing blood flow to ischemic feet through revascularization procedures, if possible.

REFERENCES

Bisno AL, Stevens DL: Streptococcal infections of skin and soft tissues. N Engl J Med 1996;334:240.

Davies HD et al: Invasive group A streptococcal infections in Ontario, Canada. N Engl J Med 1996;335:547.

Eriksson B et al: Erysipelas: clinical and bacteriologic spectrum and serological aspects. Clin Infect Dis 1996;23:1091.

Frykberg RG, Veves A: Diabetic foot infections. Diabetes/Metab Rev 1996;12:255.

Green RJ, Dafoe DC, Raffin TA: Necrotizing fasciitis. Chest 1996;110:219.

Griego RD et al: Dog, cat, and human bites. J Am Acad Dermatol 1995;33:1019.

Lewis RT: Necrotizing soft-tissue infections. Infect Dis Clin N Am 1992;6:693.