Skin and Soft Tissue Infections

Introduction

Skin and soft tissue infections (SSTIs) are among the most commonly occurring bacterial infections, and their frequency approaches 10% of hospital admissions for infections in the United States. Many factors contribute to the increase in awareness of SSTIs: the aging of the general population, the growing number of critically ill or immunocompromised patients, and the emergence of multidrug-resistant (MDR) pathogens are commonly considered the main reasons for SSTI increase in frequency and severity.

SSTIs have variable presentation, as they can range from mild to severe, life-threatening infections. Healthy hosts or compromised hosts belonging to all age groups can be affected by SSTIs, and their severity and prognosis can be related to the host condition. Many differences can be observed with respect to etiology of SSTIs that can be influenced by a number of factors. Evidence deriving from common practice demonstrates that immunologic status, previous antimicrobial treatments, geographic localization, recent history of trauma or surgery, animal exposure, and bites have to be considered in the evaluation of diagnostic and therapeutic strategies for a patient reporting an SSTI. All these considerations warrant an accurate evaluation and clinical observation of each case either to avoid the severe, life-threatening complications of undertreatment or to avoid the severe complications with overdiagnosis of SSTIs, particularly in the setting of stasis dermatitis or after venom reactions, such as honeybee stings. On the basis of a large multicenter trial of patients presenting to an emergency department, a presumptive diagnosis of cellulitis—the most common skin infection, accounting for 650,000 hospitalizations in the United States annually—was not confirmed in 30% of the patients after dermatology consultation. In these cases, venous stasis dermatitis, erythema migrans, contact dermatitis, eczema, and erythema nodosum were the most common mimics of cellulitis.

Any study on the etiologic aspect of SSTIs is hampered by the low yields of blood and skin cultures that make the microbiologic findings available for less than 30% of the patients affected by cellulitis. As a general concept, Staphylococcus aureus and β-hemolytic streptococci (BHS) are considered the most frequent causative agents of SSTIs. The majority of SSTIs report a monomicrobial etiology, and a polymicrobial etiology can be demonstrated in about 20% of the cases.

Definitions and Classifications of SSTIs

Intact skin provides an effective protection from the external environment, acting as a physical barrier and maintaining a microbiologic environment that is not conducive to the growth of pathogenic organisms. SSTIs can occur after microorganisms invade otherwise healthy skin or when an underlying disease or trauma favors the infection of damaged skin. The damage is due to the destruction of affected tissues causing an inflammatory response clinically characterized by pain, local warmth, and erythema. In particular settings, such as in patients living with diabetes mellitus or neuropathies, the degree of skin damage can be high and the management can be more complicated. In these particular settings, recurrent episodes or the evidence of nonhealing lesions suggests the need for further investigations to assess vascular and lymphatic compromise.

SSTIs represent a heterogeneous array of disorders, and a number of classifications have been proposed. Every attempt at classification organizes SSTIs on the basis of a specific variable, such as anatomic localization, etiologic agent, skin extension, progression rate, clinical presentation, and severity. Each of them has its own usefulness, but in general what the clinician expects from classifications is to be driven toward the most appropriate management of the condition. On this basis, the Infectious Diseases Society of America (IDSA) classification has been the most useful and practical guidance to date by adopting three different distinctions: (1) skin extension: uncomplicated typically superficial infections (uSSTIs) and complicated infections (cSSTIs), usually with deep involvement; (2) rate of progression: acute and chronic wound infections; and (3) tissue necrosis: necrotizing and non-necrotizing infections. However, the need to standardize the definitions of SSTI to be adopted to patients involved in pivotal trials evaluating antibiotic treatments prompted the US Food and Drug Administration (FDA) to introduce the new definition of acute bacterial skin and skin-structure infection (ABSSSI) that includes cellulitis/erysipelas, wound infections, and major cutaneous abscesses. Thus an ABSSSI is defined as a bacterial infection of the skin with a lesion size area of ≥75 cm ² (lesion size measured by the area of redness, edema, or induration). Table 12.1 provides a practical classification of SSTIs based on the anatomic structure involved, highlighting the different modality of transmission and clinical characteristics.

Table 12.1

Clinical Presentation of the Most Relevant SSTIs

SSTI	Conditioning Factors	Characteristics
Impetigo ( Fig. 12.1 )	Subjects : Children aged 2–5 yr (peak of incidence), newborns, adults in low-income areas. Atopic dermatitis is an important risk factor. Transmission : Person-to-person or via fomites. Clinically apparent 10 days after skin colonization. Localization : Exposed body areas, orifical areas, face, scalp, and the back of the hands (non-bullous impetigo); skin folds (bullous impetigo).	Nonbullous impetigo (contagious impetigo): Papules surrounded by erythema that become superficial vesicles and then pustules, which evolve to form characteristic thick, honey-colored crusts. Multiple spreading lesions (auto-inoculation). S. aureus is the most common pathogen; Streptococcus pyogenes is less common and can be either a single pathogen or in combination with S. aureus. Bullous impetigo: Caused by toxin-producing S. aureus , is a localized form of staphylococcal scalded skin syndrome. Vesicles that rapidly evolve into flaccid bullae filled with clear, yellow fluid that can become purulent.
Ecthyma	Subjects : Healthy people living in tropical areas or immunocompromised. Pathogenesis : Via small trauma, bacteria invade the skin barrier. Localization : Epidermal and dermal layers.	A vesicle or pustule overlying an inflamed area of skin that deepens into a dermal ulceration with overlying gray-yellow crust followed by a shallow, punched-out ulceration that appears when crust is removed, evolving towards a hard brown-blackish crust. Ecthyma gangrenosum : Necrotic skin ulcer, which can be a primary or secondary infection; secondary infection set in course of sepsis caused by P. aeruginosa , among immunocompromised.
Erysipelas ( Fig. 12.2 )	Subjects : Peak of incidence in childhood and over 50 yr Localization : Lower extremities (adults); face (adults and children). Course of infection : Short.	Warm and aching erythema heralded by fever, heat, and shivering. The lesion extends to surrounding areas with a sharp border. Flaccid vesicles and bullae filled with purulent fluid may appear 2–3 days after infection with lymphangitis and regional lymph node inflammation.
Cellulitis ( Fig. 12.3 )	Subjects : No target population. Localization : Face and extremities. Course of infection : Long, with frequent recurrences and local complications; S . aureus and β-hemolytic streptococci commonly involved.	Erythema, edema, warmth, and tenderness of a poorly demarked area with lymphadenopathy and fever. S. aureus and Bacteroides spp.: Cellulitis in diabetic patients. Pseudomonas spp. and Enterobacteriaceae : In hospitalized patients. Clostridium spp.: In exposed fractures and penetrating trauma. Streptococcus spp. plus Haemophilus influenzae : Orbital cellulitis, in healthy children <5 yr.
Necrotizing fasciitis (NF) ( Fig. 12.4 )	Population : Those with an infected area after chickenpox, trauma, surgery, or illegal drug use. Localization : Extremities, abdomen, perineum. Pathogenesis : Streptococcal hemolytic toxins (streptolysin O and S). Risk factors : Immunosuppression, chickenpox.	NF type 1: Polymicrobial infection, destroys subcutaneous fat and muscular fascia. NF type 2: Caused by beta-haemolytic streptococci (BHS) of Lancefield groups A, C or G alone or associated with S. aureus.
Myonecrosis (MN)	Population : Traumatologic or oncologic MN is an acute, life-threatening infection that can cause many complications, the most common being gangrene.	Gas gangrene: Slowly expanding ulceration confined to the superficial fascia; determines necrosis of muscle, gas in the tissues, and systemic toxicity; is caused by Clostridium spp. Traumatic gangrene: Presents with acute severe pain on the wound area, which becomes purple-reddish with bullae, edema, and crepitus within few days from trauma. It is associated with sepsis.

Microbiology of SSTI

The site of infection can influence microbiology. For example, facial infections are commonly caused by group A β-hemolytic streptococci (GABHS), and an increasing percentage of lower extremity infections is caused by non-GABHS such as Streptococcus agalactiae . S. aureus and BHS are the main etiologic agents of uncomplicated SSTIs; BHS is the primary cause of erysipelas.

Staphylococci sustain the majority of cases with skin abscesses, and the bacteria that constitute the normal skin flora boost their virulence. When we look at the patients affected by cellulitis, we find that GABHS or S. aureus is frequently involved. Patients with chronic venous stasis or with saphenous vein harvest for coronary artery bypass surgery experiencing recurrent cellulitis of the lower extremities report an infection caused by BHS. Similarly, recurrent episodes of cellulitis in patients with lymphedema are frequently sustained by BHS. Staphylococci and BHS are also the most common pathogens in bacterial infections among drug users. Gram-negative and anaerobic bacteria are more common in association with surgical site infections (SSIs) of the abdominal wall or infections of the soft tissue in the anal and perineal region due to the specific characteristic of the bacterial flora in these parts of the body.

Particular settings for SSIs and SSTIs can include those with cytotoxic therapy–induced granulocytopenia. In these cases, extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae and carbapenem-resistant Pseudomonas aeruginosa constitute about 10% of the etiologic agents reported in those with SSI. Patients affected by hematologic malignancies or bone marrow transplant recipients can develop “ecthyma gangrenosum”—cellulitis caused by the hematogenous seeding of P. aeruginosa , Stenotrophomonas maltophilia , and other bacteria and fungi otherwise infrequently involved in SSTIs.

Immunocompromised patients after solid-organ transplantation represent another particular setting. They can develop cellulitis due to unusual organisms, including Gram-negative bacilli, anaerobes, and other opportunistic pathogens such as Mycobacteria and fungi. Cellulitis from uncommon bacterial species, including Enterobacteriaceae , Enterococcus faecalis , Bacteroides spp . , and Clostridium spp . , can be observed after subcutaneous injections of illegal drugs. Other uncommon causes of cellulitis include Neisseria meningitidis , Mycobacterium avium , Pasteurella multocida (which is associated with animal bites), Aeromonas hydrophilia (after contact with freshwater), Chromobacterium violaceum, Vibrio vulnificus (after contact with seawater), and several other pathogens.

When we look at hospital-acquired bacteria, focusing on patients requiring intensive care, we find that Acinetobacter baumannii is the main emerging MDR pathogen causing soft tissue infections, including cellulitis, after the use of invasive devices. Current data indicate that A. baumannii can be an important pathogen in patients with burn wounds, where a high percentage of resistant strains that significantly contribute to mortality has been observed.

Necrotizing fasciitis is frequently sustained by S. aureus and GABHS, alone or in combination. Most cases are polymicrobial, Gram-positive cocci, especially S. aureus , are the main pathogens causing diabetic foot infections, but Gram-negative pathogens can be reported in those with chronic infection receiving multiple antibiotic treatments. Infections in patients suffering foot ischemia or gangrene can be caused by obligate anaerobic pathogens.

Polymicrobial infections account for about 10% of cases of SSTI, and both Gram-positive and Gram-negative organisms can be the causative agent. According to general considerations, polymicrobial infections provide a complex environment in which a variety of interactions may occur between causal pathogens that may share virulence determinants and trigger the synergistic release of cytokines, adding to the severity of the infection. Most of the polymicrobial SSTIs can be included in the following: diabetes-related foot infections (DFIs), pressure ulcer infections, burn infections, and infected chronic ulcers. These distinct clinical entities have a common characteristic in that they can become chronic with a high degree of colonization from bacteria present in the surrounding environment that can interact to increase their pathologic effects and possibly lead to resistance.

Microbiologic Diagnosis

Even though microbiologic data do not play a role in the choice of initial empiric therapy, the need for etiologic tests depends on several factors, including the type of infection, severity of the clinical condition, and the underlying patient condition. As a general concept, uncomplicated SSTIs (cellulitis or small subcutaneous abscess) do not require microbiologic investigations; instead, when exudates and abscesses are evident in a patient with complicated SSTI, specimens have to be collected. Moreover, all immunosuppressed patients and injuries contaminated with soil or animal bites have to be investigated by cultures and microscopic examination of cutaneous aspirates or biopsies.

Diagnostic workup of SSTI differs with respect to patient condition and infection severity. Blood cultures have to be attempted for all cases with severe infection requiring hospitalization. Cultures and microscopic examination of cutaneous aspirates, pus, biopsies, or swabs should be considered in complex infection, septic and immunosuppressed patients, water- or soil-related injuries, and animal bites. It is important to emphasize that superficial swabs of open ulcers and drainage from fistulous material usually do not correctly identify the microbiologic etiology. In fact, in patients with deep tissue infections, the results of superficial techniques do not reflect the etiologic pathogen because of the presence of commensal microorganisms on the wound surface, which explains the low specificity of the diagnostic investigation. Quantitative cultures have been proposed to distinguish commensal microbiota from clinically significant bacterial growth, but the usefulness of this technique has been questioned by numerous prospective studies.

Blood cultures are positive in a percentage of cases, approaching 5%. Cultures attempted from materials derived from needle aspirations of the inflamed skin are positive in an extremely variable number of cases (<5% to 40%, on the basis of the different studies available by a literature analysis). Cultures of punch biopsy specimens yield an organism in 20% to 30% of cases. If an abscess is present, puncture and aspiration of fluid should be performed. SSTIs without any evidence of liquid collection have to be investigated by a small biopsy of skin or soft tissue after superficial disinfection and excision of necrotic tissue. Chronic wounds can be investigated by pus or fluid culture; alternative samples to biopsy include aspiration of saline that has just been infused into the wound depth.

Molecular technologies can be considered an effective, time-saving alternative to overcome the delay in the results associated with traditional bacterial culture. Polymerase chain reaction (PCR)–based techniques are equally sensitive as cultures, but can be useful for the diagnosis of SSTIs sustained by S. aureus , potentially providing crucial information as to the choice of appropriate antibiotic regimen, such as the rapid detection of Panton–Valentine leucocidin-encoding genes from pus samples or the identification of cryptic resistances.

Imaging Studies

Imaging studies are sometimes required to establish an accurate diagnosis of SSTI. Plain radiography can help in detecting the presence of gas in the soft tissues, which is suggestive of a necrotizing infection, or in diagnosing an osteomyelitis. Computed tomography (CT) scans can give useful information and help to assess the extent of the infectious process, guiding fluid aspiration and revealing the presence of foreign objects or even small fluid–air collections in the soft tissues. Magnetic resonance imaging (MRI) has the advantage of a better definition of soft tissues and can be particularly helpful in differentiating cellulitis from pus and abscess formation. Moreover, MRI provides better accuracy than CT in detecting necrosis, inflammatory edema, and muscular fascia involvement, but its use is limited because of its cost. Ultrasonography can be a sensitive technique for SSTI diagnosis, reporting important advantages over other imaging studies, including MRI. In fact, ultrasonography provides useful information to differentiate cellulitis from abscess, therefore limiting more expensive imaging studies and unnecessary harmful procedures like incision and drainage. Moreover, ultrasonography is an easy and rapid technique without side effects and high costs that can be performed in many cases where MRI cannot be performed. Radionuclide scanning studies generally lack specificity in the acute situation, but the development of hybrid techniques (such as single-photon emission tomography [SPECT]/CT and positron emission tomography [PET]/MRI) can increase the specificity of nuclear medicine imaging techniques, eventually revealing the involvement of surrounding structures.

Indications for Hospital Admission

SSTIs are among the most common reasons for hospitalization of adults in the United States. Several authors have attempted to identify indications for hospital admission for patients with SSTI. Medical history, presence of fever or relevant comorbidities (e.g., vascular insufficiency, neuropathy, diabetes, and immunosuppression), the site of the lesion itself (the hand or head has the potential for more significant damage), particular aspects of laboratory investigations (e.g., elevated white blood cell count and lactate levels), and the degree of involvement of the body surface (>9%) have to be considered to establish the necessity for hospital admission. Overall, the large majority of patients with uncomplicated SSTIs can be managed as outpatients. However, complicated infections often require hospital admission, especially if muscle or fascial involvement is suspected, the process is rapidly progressing, signs of toxemia are developing, the diagnosis or prognosis is in doubt, exploratory surgery is contemplated, or the patient cannot adequately comply with outpatient treatment.

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