**8. Management of MRSA bacteremia and infective endocarditis in adults**

MRSA was described in 1961, shortly after methicillin was introduced. Unlike penicillin resistance, which is achieved via the bacteria‐produced enzyme penicillinase, methicillin resistance is mediated by a newly acquired penicillin‐binding protein (called PBP2A) and encoded for by the *mecA* gene. The *MecA* gene is located on a mobile genetic element called staphylococcal chromosome cassette (SCCmec) [14]. If methicillin‐resistant *S. aureus* bacte‐ remia is identified, vancomycin and daptomycin are generally recommended for treatment based on current guidelines. Glycopeptides are a class of antibiotics that include vancomycin and work by binding to bacterial cell wall precursors and interfering with penicillin‐binding protein enzymes, causing cessation of cell wall synthesis and later cell death. Daptomycin is a lipopeptide that is approved for the treatment of *S. aureus‐*complicated skin or soft tis‐ sue infection, bacteremia and right‐sided infective endocarditis [15]. Daptomycin diffuses through the peptidoglycan layer of Gram‐positive organisms to the plasma membrane where it caused rapid depolarization resulting in the loss of membrane potential leading to loss of protein, DNA, and RNA synthesis and resulting in cell death [16].

In the case of uncomplicated bacteremia that is determined by the absence of endocarditis, artificial hardware, multiple sites of infection, and for which repeated blood cultures do not grow MRSA and patients are clinically well, vancomycin or daptomycin 6 mg/kg/dose IV once daily can be given for at least 2 weeks. However, in the case of complicated bacteremia, a duration of 4–6 weeks of therapy is recommended, depending on the extent of infection. Sometimes, higher dosages of daptomycin at 8–10 mg/kg/dose IV once daily may be needed.

When MRSA bacteremia becomes complicated with infective endocarditis, IV vancomycin or daptomycin 6–10 mg/kg/dose IV once daily for 6 weeks is recommended. It is not recom‐ mended to add gentamicin or rifampin to vancomycin for bacteremia or native valve infective endocarditis.

It is also important to identify the source and extent of the infection with removal and debride‐ ment or drainage of other sites of infection to decrease the bulk of the infection. Blood cul‐ tures need to be collected every 2–4 days after initial positive cultures until documentation of the clearance of bacteremia. And echocardiography is recommended for all adult patients with bacteremia to eliminate the possibility of associated endocarditis; transesophageal echo‐ cardiography (TEE) being preferred over transthoracic echocardiography (TTE). In the cases of large vegetations that exceed 10 mm in diameter, occurrence of more than one embolic event during the first 2 weeks of therapy, severe valvular insufficiency, valvular perforation or dehiscence, decompensated heart failure, perivalvular or myocardial abscess, new heart block, or persistent fevers or bacteremia, evaluation for replacement of the affected valve should be considered in consultation with cardiothoracic surgery.

In conditions that are characterized by MRSA bacteremia complicated with infective endocar‐ ditis of a prosthetic valve, administration of IV vancomycin plus rifampin 300 mg PO/IV every 8 h for at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h for 2 weeks is recommended, along with early evaluation for valve replacement surgery to decrease the risk of embolization.
