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Staphylococcus
Staphylococci are hardy, aerobic, gram-positive bacteria that grow in pairs and clusters and are ubiquitous as normal flora of humans and present on fomites and in dust. They are resistant to heat and drying and may be recovered from nonbiologic environments weeks to months after contamination. Strains are classified as Staphylococcus aureus if they are coagulase positive or as one of the many species of coagulase-negative staphylococci (e.g ., Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus haemolyticus ). S. aureus has many virulence factors that mediate various serious diseases, whereas coagulase-negative staphylococci tend to be less pathogenic unless an indwelling foreign body (e.g., intravascular catheter) is present. S. aureus strains resistant to β-lactam antibiotics, typically referred to as methicillin-resistant Staphylococcus aureus (MRSA) , have become a significant problem in both community and hospital settings.
Staphylococcus aureus
Staphylococcus aureus is the most common cause of pyogenic infection of the skin and soft tissues. Bacteremia (primary and secondary) is common and can be associated with or can result in osteomyelitis, suppurative arthritis, pyomyositis, deep abscesses, pneumonia, empyema, endocarditis, pericarditis, and rarely meningitis. Toxin-mediated diseases , including food poisoning, staphylococcal scarlet fever, scalded skin syndrome, and toxic shock syndrome (TSS), are caused by certain S. aureus strains.
Etiology
Strains of S. aureus can be identified and characterized by the virulence factors they produce. These factors tend to play 1 or more of 4 pathogenic roles in human disease: S. aureus protecting the organism from host defenses, localizing infection, causing local tissue damage, and affecting noninfected sites through toxin elaboration.
Most strains of S. aureus possess factors that protect the organism from host defenses. Many staphylococci produce a loose polysaccharide capsule, or biofilm , which may interfere with opsonophagocytosis. Production of clumping factor and coagulase differentiates S. aureus from coagulase-negative staphylococci. Clumping factor interacts with fibrinogen to create large clumps of organisms, interfering with effective phagocytosis. Coagulase causes plasma to clot by interacting with fibrinogen and may have an important role in abscess formation. Protein A is located on the outermost coat of the cell wall and can absorb serum immunoglobulins, preventing antibacterial antibodies from acting as opsonins and thus inhibiting phagocytosis. The staphylococcal enzyme catalase inactivates hydrogen peroxide, promoting intracellular survival.
Many strains of S. aureus produce substances that cause local tissue destruction. A number of immunologically distinct hemolysins that act on cell membranes and cause tissue necrosis have been identified (α-toxin, β-hemolysin, δ-hemolysin). Much attention has been given to the Panton-Valentine leukocidin, a protein that S. aureus combines with phospholipid in the leukocytic cell membrane, producing increased permeability and eventual death of the cell. Strains of S. aureus that produce Panton-Valentine leukocidin are associated with more-severe and invasive skin disease, pneumonia, and osteomyelitis. Many strains of S. aureus release 1 or more exotoxins. Exfoliatins A and B are serologically distinct proteins that produce localized (bullous impetigo) or generalized (scalded skin syndrome, staphylococcal scarlet fever) dermatologic manifestations (see Chapter 685 ).
S. aureus can produce >20 distinct enterotoxins (types A-V). Ingestion of preformed enterotoxin, particularly types A or B, can result in food poisoning , resulting in vomiting and diarrhea and, in some cases, profound hypotension.
Toxic shock syndrome toxin-1 (TSST-1) is associated with toxic shock syndrome (TSS) , related to menstruation and focal staphylococcal infection (see Chapter 208.2 ). TSST-1 is a superantigen that induces production of interleukin (IL)-1 and tumor necrosis factor (TNF), resulting in hypotension, fever, and multisystem involvement. Focal infections associated with enterotoxins A or B also may be associated with nonmenstrual TSS.
S. aureus also possesses intrinsic factors that can contribute to pathogenesis, including proteins that promote adhesion to fibrinogen, fibronectin, collagen, and other human proteins. Expression of proteins that mediate antibiotic resistance is also of critical importance. Although historically sensitive to penicillin, S. aureus isolates now almost universally produce penicillinase or β -lactamase , which inactivates many β-lactamases at the molecular level and represents the major resistance mechanism against many penicillin and cephalosporin antibiotics. Thus, treatment of S. aureus with β-lactam antibiotics requires either a penicillinase resistant β-lactam ring or combination with a β-lactamase inhibitor. Production of altered penicillin-binding proteins (PBPs) in the bacterial cell wall mediates resistance to penicillinase resistant antibiotics: an altered PBP-2A , encoded by the gene MECA , is responsible for the methicillin and cephalosporin resistance of MRSA isolates.
Epidemiology
Approximately 20–40% of normal individuals carry at least 1 strain of S. aureus in the anterior nares at any given time, with intermittent carriage occurring in up to 70% of individuals. The organisms may be transmitted from the nose to the skin, where colonization is more transient. Persistent umbilical, vaginal, and perianal carriage may also occur. Many neonates are colonized within the 1st week of life, usually by a maternal strain. Rates of colonization with MRSA in the general pediatric population are typically <2% but may be higher in some locales and in children with significant healthcare exposure and chronic medical conditions.
Exposure to S. aureus generally occurs by autoinoculation or direct contact with the hands of other colonized individuals. Heavily colonized nasal carriers (often aggravated by a viral upper respiratory tract infection) are particularly effective disseminators. Spread by fomites is rare, although an outbreak occurring in a high school football team was attributed to sharing towels. Infection control policies in healthcare facilities, particularly those emphasizing good hand hygiene, have been shown to decrease rates of nosocomial staphylococcal infection.
Outside the hospital setting, outbreaks of staphylococcal disease, in particular disease caused by methicillin-resistant strains, have been reported among athletes, military personnel, young children, veterinarians, injection drug users, and inmates in correctional facilities. Increased disease frequency is noted among household contacts of a MRSA-colonized or infected individual. Skin infections caused by S. aureus are considerably more prevalent among persons living in low socioeconomic circumstances and particularly among those in tropical climates.
The burden of staphylococcal disease is significant. Most important is the role of S. aureus, including MRSA, in hospital-acquired infections , including infections of the bloodstream, infection of surgical sites, and ventilator-associated pneumonia. S. aureus is a significant cause of morbidity and mortality in neonatal intensive care units (NICUs). Community-acquired staphylococcal infections are estimated to result in 14 million annual outpatient healthcare visits. In 2005 an estimated 478,000 hospitalizations were associated with S. aureu s infection in the United States, more than half of which were caused by MRSA. Recent evidence shows a decline in rates of invasive MRSA infection in adults, but an opposite trend in U.S. pediatric patients was noted in 2013.
Pathogenesis
Except in the case of food poisoning resulting from ingestion of preformed enterotoxins, disease associated with S. aureus typically begins with colonization as previously described. Subsequent disease manifestations in susceptible individuals result either directly from tissue invasion or from injury caused by various toxins and enzymes produced by the organism ( Fig. 208.1 ).
The most significant risk factor for the development of infection is disruption of intact skin , including breaches from wounds, skin disease such as eczema, epidermolysis bullosa or burns, ventriculoperitoneal shunts, and indwelling intravascular or intrathecal catheters. Additional risk factors include corticosteroid treatment, malnutrition, and azotemia. Antibiotic therapy with a drug to which S. aureus is resistant favors colonization and the development of infection. Viral infections of the respiratory tract, especially influenza virus, may predispose to secondary bacterial infection with staphylococci in certain individuals.
Congenital defects in chemotaxis (e.g., Job, Chédiak-Higashi, and Wiskott-Aldrich syndromes) and defective phagocytosis and killing (e.g., neutropenia, chronic granulomatous disease) increase the risk for staphylococcal infections. Patients with HIV infection have neutrophils that are defective in their ability to kill S. aureus in vitro. Patients with recurrent staphylococcal infection should be evaluated for immune defects, especially those involving neutrophil dysfunction. Poor mucous clearance in children with cystic fibrosis frequently leads to chronic staphylococcal colonization and persistent inflammation in these patients.
Infants may acquire type-specific humoral immunity to staphylococci transplacentally. Older children and adults develop antibodies to staphylococci as a result of colonization or minor infections. Antibody to the various S. aureus toxins appears to protect against those specific toxin-mediated diseases, but humoral immunity does not necessarily protect against focal or disseminated S. aureus infection with the same organisms.
Clinical Manifestations
Signs and symptoms vary with the location of the infection, which is usually the skin but may be any tissue. Disease states of various degrees of severity are generally a result of local suppuration, systemic dissemination with metastatic infection, or systemic effects of toxin production.
Newborn
S. aureus is an important cause of neonatal infections (see Chapter 129 ).
Skin
S. aureus is an important cause of pyogenic skin infections, including impetigo contagiosa, ecthyma, bullous impetigo, folliculitis, hydradenitis, furuncles (boils), carbuncles (multiple coalesced boils), and paronychia. Toxigenic infection with skin manifestations include staphylococcal scalded skin syndrome and staphylococcal scarlet fever. S. aureus is a frequent cause of superinfection of underlying dermatologic conditions, such as eczema or bug bites. Recurrent skin and soft tissue infections often are noted with community-associated MRSA and affect the lower extremities and buttocks. S. aureus is also an important cause of traumatic and surgical wound infections and can cause deep soft tissue involvement, including cellulitis and rarely, necrotizing fasciitis.
Respiratory Tract
Infections of the upper respiratory tract (otitis media, sinusitis) caused by S. aureus are rare, in particular considering the frequency with which the anterior nares are colonized. S. aureus sinusitis is relatively common in children with cystic fibrosis or defects in leukocyte function and may be the only focus of infection in some children with TSS. Suppurative parotitis is a rare infection, but S. aureus is a common cause. A membranous tracheitis that complicates viral croup may result from infection with S. aureus, although other organisms may also be responsible. Patients typically have high fever, leukocytosis, and evidence of severe upper airway obstruction. Direct laryngoscopy or bronchoscopy shows a normal epiglottis with subglottic narrowing and thick, purulent secretions within the trachea. Treatment requires careful airway management and appropriate antibiotic therapy.
Pneumonia caused by S. aureus may be primary or secondary after a viral infection such as influenza (see Chapter 428 ). Hematogenous pneumonia may be secondary to septic emboli from right-sided endocarditis or septic thrombophlebitis, with or without intravascular devices. Inhalation pneumonia is caused by alteration of mucociliary clearance, leukocyte dysfunction, or bacterial adherence initiated by a viral infection. Common symptoms and signs include high fever, abdominal pain, tachypnea, dyspnea, and localized or diffuse bronchopneumonia or lobar disease. S. aureus often causes a necrotizing pneumonitis that may be associated with early development of empyema, pneumatoceles, pyopneumothorax, and bronchopleural fistulas. Chronic pulmonary infection with S. aureus contributes to progressive pulmonary dysfunction in children with cystic fibrosis (see Chapter 432 ).
Sepsis
S. aureus bacteremia and sepsis may be primary or associated with any localized infection. The onset may be acute and marked by nausea, vomiting, myalgia, fever, and chills. Organisms may localize subsequently at any site (usually a single deep focus) but are found especially in the heart valves, lungs, joints, bones, muscles, and deep tissue abscesses.
In some instances, especially in young adolescent males, disseminated S. aureus disease occurs, characterized by fever, persistent bacteremia despite antibiotics, and focal involvement of 2 or more separate tissue sites (skin, bone, joint, kidney, lung, liver, heart). These patients often have an endovascular nidus of infection, such as an infected venous thrombosis.
Muscle
Localized staphylococcal abscesses in muscle sometimes without septicemia have been called pyomyositis. This disorder is reported most frequently from tropical areas and is termed tropical pyomyositis, but also occurs in the United States in otherwise healthy children. Multiple abscesses occur in 30–40% of cases. History may include prior trauma at the site of the abscess. Surgical drainage and appropriate antibiotic therapy are essential.
Bones and Joints
S. aureus is the most common cause of osteomyelitis and suppurative arthritis in children (see Chapters 704 and 705 ).
Central Nervous System
Meningitis caused by S. aureus is uncommon; it is associated with penetrating cranial trauma and neurosurgical procedures (craniotomy, cerebrospinal fluid [CSF] shunt placement), and less frequently with endocarditis, parameningeal foci (epidural or brain abscess), complicated sinusitis, diabetes mellitus, or malignancy. The CSF profile of S. aureus meningitis is indistinguishable from that in other forms of bacterial meningitis (see Chapter 621.1 ).
Heart
S. aureus is a common cause of acute endocarditis on native valves and results in high rates of morbidity and mortality. Perforation of heart valves, myocardial abscesses, heart failure, conduction disturbances, acute hemopericardium, purulent pericarditis, and sudden death may ensue (see Chapter 464 ).
Kidney
S. aureus is a common cause of renal and perinephric abscess, usually of hematogenous origin. Pyelonephritis and cystitis caused by S. aureus are unusual (see Chapter 553 ).
Toxic Shock Syndrome
S. aureus is the principal cause of TSS, which should be suspected in anyone with fever, shock, and/or a scarlet fever–like rash (see Chapter 208.2 ).
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