**6. Bacteremia caused by** *S. aureus*

Bacteremia is defined as the presence of bacteria in normally sterile blood. Typically more than one bottle in the set will be positive for growth; however, only one positive bottle is needed to diagnose bacteremia. Risk factors associated with *S. aureus* bacteremia include the presence of prosthetic devices, surgical site infections, or skin conditions such as chronic ulceration, injection drug use (IDU), and host factors that incur predisposition to recurrent infections. Prosthetic devices include any intravascular catheter such as hemodialysis catheter or central venous catheter. Patients on hemodialysis are at a higher risk for staphylococcal endocarditis and constitute a relatively new at‐risk group. Other factors include defects of polymorphonuclear leukocytes and congenital syndromes that are associated with more risk of *S. aureus* infections, such as the cases of neutropenia, chronic granulomatous disease, as well as Job's, Chediak‐Higashi, and Wiskott‐Aldrich [3].

Clinical manifestations of *S. aureus* bacteremia typically involve systemic responses such as fever and hypotension. When bacteremia occurs secondarily to infection at a primary site, clinical symptoms associated with that organ system may also be present. Cellulitis, chronic ulceration, or trauma to skin and soft tissue may serve as portals of entry for the bacteria and the primary source of a *S. aureus* bacteremia. Tenderness or erythema surrounding a vascular catheter may also serve as a clinical manifestation of underlying bacteremia [4], though absence does not rule out the diagnosis. Patients with *S. aureus* pneumonia can develop bacteremia and have accompa‐ nying upper respiratory symptoms. *S. aureus* bacteriuria without the presence of a urinary cath‐ eter may be an indicator of *S. aureus* bacteremia [5]. *S. aureus* meningitis, though less common, may also occur in the setting of complication due to *S. aureus* bacteremia [6] and in addition to fever can demonstrate confusion and nuchal rigidity associated with acute bacterial meningitis.

Clinical approach to a patient with *S. aureus* bacteremia should include a detailed history, thor‐ ough physical exam, and if required, additional imaging with possible infectious disease con‐ sultation. History should involve questions as to the presence or absence of potential portals of entry such as wounds and also determine the presence of prosthetic devices including hardware (orthopedic or cardiac) and intravascular catheters. Questions related to localization of pain may help determine if metastatic spread has occurred such as in cases of vertebral osteomyeli‐ tis/diskitis or endocarditis. Physical exam should include an extensive evaluation of the skin and mucous membranes to look for sites of bacterial entry. Cardiac evaluation should assess for the presence of murmurs associated with infective endocarditis. Other stigmata of endocar‐ ditis should be sought through fundoscopic exam and exam of the digits for the appearance of emboli in skin. Baseline mental status should be noted and carefully monitored for signs of deterioration which may be concomitant with development of additional complications.

Complications of *S. aureus* bacteremia range from colonization after a treatment to infective endocarditis. Infective endocarditis is one of the most severe complications, with *S. aureus* now recognized as the most common cause in the industrialized world [7]. Pathogenesis is due to a combination of adhesion factors (as discussed earlier) on the surface of *S. aureus* and bacterial‐induced platelet aggregation, which cause adhesion damage to heart valves [8]. Risk factors for IE in the setting of *S. aureus* bacteremia include prosthetic heart valve or pre‐ disposing cardiac abnormalities, IVDU, intravascular catheter infection, or persistent bac‐ teremia [9]. Specific clinical manifestations associated with *S. aureus* infective endocarditis include sepsis syndrome involving fever, tachycardia, and hypotension, cardiac failure due to valve destruction, and sequelae from septic emboli. Within the heart, once *S. aureus* adheres to and colonizes the valve its intrinsic procoagulant activity triggers deposition of platelets and fibrin which leads to the formation of a vegetation. The structural abnormality is typically associated with regurgitation, and if untreated can progress to cardiac failure. Transthoracic echocardiography should be used as the initial diagnostic test in a patient with suspected endocarditis, as its specificity approaches 100% [10], however, specificity is lower being at most 75%. Transthoracic echocardiography is not 100% specific for infective endocarditis due to potential false positives, however, given a sensitivity greater than 90%, it is the better of the two for identification of valvular vegetations. Vascular phenomena occur when septic emboli dislodge from the vegetation and occlude arteries in the periphery as well as centrally affecting vital organs. Peripheral manifestations including skin lesions (Janeway spots, Osler's nodes) and retinal lesions (Roth's spots), while splenic vein thrombosis can lead to infarction of the spleen. Neurological complications include cerebral infarctions, intracerebral or sub‐ arachnoid hemorrhage, meningitis, cerebritis, and encephalomalacia.
