Anti-Clumping Factor A Immunoglobulin Reduces the Duration of Methicillin-ResistantStaphylococcus aureusBacteremia in an Experimental Model of Infective Endocarditis

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Abstract
SA-IGIV is a human polyclonal immunoglobulin containing elevated levels of antibodies specific for the fibrinogen-binding MSCRAMM protein clumping factor A (ClfA). In vitro, SA-IGIV specifically recognized ClfA that was expressed on the surface ofStaphylococcus aureusand inhibited bacterial adherence to immobilized human fibrinogen by >95%. Moreover, SA-IGIV efficiently opsonized ClfA-coated fluorescent beads and facilitated phagocytosis by human polymorphonuclear leukocytes. To determine its potential therapeutic efficacy, SA-IGIV was evaluated in combination with vancomycin in a rabbit model of catheter-induced aortic valve infective endocarditis (IE) caused by methicillin-resistantS. aureus(MRSA). The combination therapy was more effective than vancomycin alone in sterilizing all valvular vegetations when used therapeutically during early (12-h) IE. The combination therapy resulted in clearance of bacteremia that was significantly faster than that of vancomycin alone in animals with well-established (24-h) IE. Therefore, in both early and well-established MRSA IE, the addition of SA-IGIV to a standard antibiotic regimen (vancomycin) increased bacterial clearance from the bloodstream and/or vegetations.

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