Staphylococci are gram-positive, nonmotile, aerobic, or facultative anaerobic bacteria. They are not fastidious and grow well on ordinary media. All members are catalase-positive. Staphylococci are categorized by their ability to produce coagulase; S. aureus is coagulase-positive. Currently, 29 species are CoNS. S. aureus and some CoNS produce a capsule for which the clinical importance is unclear, but it is the basis of a vaccine strategy currently being tested. S. aureus produces a unique cell wall protein, protein A, that possesses antiphagocytic properties and has a high affinity for the Fc portion of certain immunoglobulin subclasses.

Coagulase-positive staphylococci elaborate numerous extracellular toxins that generally are thought to be responsible for the virulence of these organisms. The clinically important staphylococcal extracellular products include the following: alpha-, beta-, and delta-hemolysins; coagulases; leukocidin; hyaluronidase; staphylokinase; the epidermolytic toxins; erythrogenic toxins; toxic shock syndrome (TSS) toxin 1 (TSS-1); and enterotoxins.

Staphylococci are widely distributed in nature and are common inhabitants of the normal human flora. S. aureus is found in the nares, fingernails, and, occasionally, skin. Nasal colonization is a risk factor for development of infection in hospitalized
patients. Neonates become colonized early in life. S. aureus is carried by 20% to 40% of adults; 30% are long-term carriers.

Staphylococci usually are tolerated by the human body; they cause localized disease (e.g., in patients with open wounds or those with an intravenous catheter) or systemic infections in immunocompromised individuals (e.g., patients who are immunosuppressed or have diabetes mellitus). Viral respiratory infection may alter the natural host defense and allow the development of staphylococcal pneumonia. Recurrent staphylococcal infections can be caused by autoinfection from an asymptomatic carrier state.

Staphylococcal infections can occur as an epidemic or as a sporadic event. Person-to-person spread (particularly via the hands) appears to be the most common form of transmission, although airborne transmission can occur. Contact with contaminated objects also may spread infection.

The pathologic effects on S. aureus can be attributed to direct tissue invasion or toxin production and liberation. Colonization factors allow S. aureus to adhere to host fibrinogen, fibronectin, laminin, collagen, and other surface-binding proteins. Binding to fibrinogen also allows S. aureus to bind to indwelling foreign bodies. Evasion of host defenses can be caused by staphylococcal protein A, teichoic acid, and, rarely, a capsule.

Some enzymes and toxins produced by S. aureus are known virulence factors. Enzymes involved in the pathogenesis include catalase, hyaluronidase, beta-lactamase, lipase, and fatty acid–modifying enzyme. Hyaluronidase or spreading factor facilitates spread of infection in the early stages. beta-Lactamase inactivates a class of antibiotics. Catalase converts hydrogen peroxide (H₂O₂) to water and oxygen, reducing H₂O₂ as a host defense mediator in phagocytosis. Lipase facilitates invasion.

S. aureus produces a variety of toxins, five of which are membrane-damaging toxins (alpha, beta, delta, and the leukocidins). Other toxins include the enterotoxins A through E, epidermolytic toxins A and B, and TSS–1. Leukocidins have several biologic effects, but their foremost action is the lysis of macrophages. The enterotoxins cause foodborne diseases; however, enterotoxins B and C are associated with TSS. The epidermolytic toxins cause scalded skin syndrome and divide the epidermis at the stratum granulosum layer. Most cases of TSS are associated with TSS-1.

The polymorphonuclear leukocyte appears to be the most important line of defense after the skin barrier has been breached. Inherited or acquired defects in chemotaxis, opsonization, or intracellular killing predispose to development of staphylococcal infection, and the incidence of such infections is highest in patients with defects in this area of host defense. Granulocytopenia of any origin predisposes to development of infection with endogenous bacteria, including staphylococci.

The formation of an abscess is characteristic of staphylococcal infections in humans, and the skin is the usual portal of entry. Tissue necrosis of the lesion occurs. Invasion and spread of the organism are promoted by increased connective tissue permeability secondary to local multiplication and the production of enzymes. Liquefaction necrosis occurs rapidly, with a fibrin wall surrounding a center of organisms and leukocytes. Thrombosis of blood vessels with formation of fibrin clots can occur. Trauma that breaks the fibroelastic barrier may spread the infection, often initiating bacteremia with spread to bones, joints, heart valves, and so forth.

The clinical manifestations vary with the portal of entry of the organism and the immune status and general health of the patients. S. aureus infections of the skin are among the most common bacterial infections. Lesions include impetigo, bullous impetigo, folliculitis, furuncles (i.e., boils), carbuncles, paronychia, cellulitis, ecthyma, staphylococcal scalded skin syndrome, staphylococcal scarlatiniform eruption, and TSS. These last three are toxin-mediated.

Musculoskeletal infections commonly are caused by S. aureus, the most frequent cause of acute osteomyelitis and discitis. In most cases, the bacteria reach the bone by hematogenous spread from a skin lesion, but they also can do so from a contiguous focus of infection. The organism usually localizes in the metaphyseal end of a long bone. The clinical syndrome may be preceded by trauma, pyoderma, or other antecedent infection. Osteomyelitis is associated with irritability, fever, anorexia, vomiting, local warmth, and point tenderness.

Staphylococcal bacteremia usually occurs with a focus of infection. Sources of bacteremia vary and often are obscure, but the skin, respiratory tract, or intravenous access should be considered. Bacteremia may have an acute onset or may be slowly progressive, with shaking chills, fever, and metastatic abscess in organs such as the lung, bone, joints, kidneys, heart, brain, or deep tissues.

Pyarthrosis also is caused frequently by S. aureus and most commonly involves the hip, knee, ankle, and elbow. Muscle abscesses usually present with a subacute onset of moderate muscle pain, followed by fever. An associated increase in serum muscle enzymes without evidence of septicemia occurs. These muscle abscesses are seen more often in tropical areas (i.e., tropical pyomyositis) but have been described in the United States with increased frequency in recent years.

Peritonsillar abscess, purulent conjunctivitis, otitis media, retropharyngeal abscess, sinusitis, acute mastoiditis, bacterial tracheitis, and parotitis can be caused by S. aureus either alone or with other bacteria. Staphylococcal pneumonia must occur as a primary infection or secondary to a viral infection. This illness begins as an upper respiratory tract infection with fever, nasal discharge, cough, and anorexia, with progression to symptoms and signs of increasing cough, tachypnea, dyspnea, and retractions. Radiographic findings associated with staphylococcal pneumonia include pneumatocele, empyema, pneumothorax, abscesses, and consolidation. Other head and neck infections caused by S. aureus include thyroiditis, cervical adenitis, orbital cellulitis, blepharitis, and hordeolum.

Visceral findings of staphylococcal infections can include hepatic, renal, perinephric, spleen, or pancreas abscesses. These abscesses can be difficult to diagnose if symptoms are nonspecific. Diffuse proliferative glomerulonephritis is a renal manifestation of staphylococcal bacteremia that is not thought to be associated with actual bacterial seeding of the kidney.

Staphylococcal enterocolitis is food poisoning caused by ingestion of contaminated food. When left at room temperature, certain foods (e.g., dairy products, bakery products, meats) are fertile soil for the production of enterotoxins. The illness has a sudden onset, occurring 1 to 6 hours after ingestion of preformed toxin in contaminated food. The illness is manifested by profuse diarrhea, abdominal cramps, and nausea. Symptoms improve within 8 to 24 hours. Staphylococcal enterocolitis also can be caused by bacterial overgrowth in the bowel after undergoing antibiotic therapy. The symptoms are the same as those of food poisoning, with the addition of fever.

Central nervous system (CNS) infections that may be caused by S. aureus include meningitis, brain subdural-epidural abscesses, and cerebral venous thrombosis. Meningitis caused by S. aureus is a rare occurrence and generally results from
hematogenous spread after surgery in patients with a foreign body, but it can occur by contiguous extension of otitis media, sinusitis, mastoiditis, or osteomyelitis of the skull and vertebrae.

Cardiovascular infections include endocarditis, pericarditis, and septic thromboses. Endocarditis is manifested by high fever, progressive anemia, and metastatic abscesses and has a high mortality rate.

S. aureus is the second most frequent cause of infections in foreign body infections after Staphylococcus epidermidis, attributable to such items as central venous catheters, CNS shunts, and peritoneal dialysis catheters. These infections often require removal of the foreign body. Infection by S. aureus in neonates includes omphalitis, breast abscess, parotitis, and cervical adenitis.

Methicillin-resistant S. aureus (MRSA) first was identified as a nosocomial pathogen. However, in recent years, strains of MRSA have emerged as distinct community-acquired organisms (CA-MRSA) with increasing prevalence. MRSA is considered community acquired if a positive culture is isolated from an outpatient or within 72 hours of hospitalization, and if risk factors for nosocomial MRSA are absent. These risk factors include a history of (a) frequent or recent hospitalization or surgery, (b) dialysis, (c) indwelling device or catheter, or (d) residence in a long-term facility. Accurate identification of CA-MRSA is hindered by inconsistent awareness of among health care providers, varying definitions, and availability of historical data.

CA-MRSA initially was described in the 1980s but has been increasingly identified, especially in the United States. At a Chicago hospital, CA-MRSA increased about 25-fold in a 5-year period, whereas other, more recent studies estimate a more modest increase. Polymerase chain reaction analysis of CA-MRSA reveals a unique gene, SCCmec IV, which codes for its methicillin resistance. It differs from the SCCmec types I-III found in nosocomial MRSA and suggests development of a novel clone rather than extension of nosocomial MRSA to the community. Although nosocomial MRSA often is multidrug resistant, most non-beta-lactam antibiotics remain effective against CA-MRSA. Studies have shown that most CA-MRSA is susceptible to clindamycin, trimethoprim-sulfamethoxazole, gentamicin, and vancomycin. Both nosocomial MRSA and CA-MRSA have a high resistance to erythromycin. However, when the D-test is performed on erythromycin-resistant, clindamycin-sensitive CA-MRSA, inducible clindamycin resistance is rare.