**7. Bacteremia treatment**

polymorphonuclear leukocytes and congenital syndromes that are associated with more risk of *S. aureus* infections, such as the cases of neutropenia, chronic granulomatous disease,

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

as well as Job's, Chediak‐Higashi, and Wiskott‐Aldrich [3].

122 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

Treatment of *S. aureus* bacteremia should first be approached by seeking out a potential focus of infection and determining whether or not it can be removed. Though no specific guidelines exist regarding duration of treatment, the general consensus advocates a 14‐day treatment course for *S. aureus* bacteremia in cases where the source such as an intravascular catheter or prosthetic device can be removed, or an abscess can be drained [11]. In cases where removal of an intravascular catheter is not possible, antibiotic lock therapy may be used in an attempt to salvage the line, which includes filling the catheter lumen with high concentrations of antibiotics and leaving them in place for several hours to days [12]. Longer treatment courses extending for 4–6 weeks are required for deeper wound infections such as endocarditis and osteomyelitis. Methicillin‐resistant *S. aureus* coverage should be included in empiric therapy with de‐escalation to a beta‐lactam agent if methicillin‐susceptible *S. aureus* is later identified.

Once *S. aureus* susceptibility is determined, antibiotic therapy may be directed toward either MSSA or MRSA. Beta‐lactams such as penicillins and cephalosporins, and if needed, glyco‐ peptides, are antibiotics classes used for the treatment of MSSA. Beta‐lactams inhibit bacterial cell wall assembly by binding to membrane bound enzymes called penicillin‐binding proteins that perform cross‐linking. The beta‐lactam ring binds to the penicillin‐binding proteins and prevents the cross‐linking component of cell wall assembly, causing cell death via autolysis of osmotic instability [13]. In cases where beta‐lactams cannot be used to treat MSSA, such as with history of anaphylaxis to penicillin, the class of antibiotics known of as glycopeptides (which includes vancomycin) may be used. It should not be used as primary treatment for MSSA, however, if drug intolerance is not an issue.

Since MRSA bacteremia constitutes a great deal of infection in this day and constitutes a major cause of increasing morbidity and mortality, we decided to elaborate more about its treatment in different settings and to discuss the newer treatment options that are available.
