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Antimicrobial Agents and Chemotherapy, November 2003, p. 3400-3406, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3400-3406.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Anti-Clumping Factor A Immunoglobulin Reduces the Duration of Methicillin-Resistant Staphylococcus aureus Bacteremia in an Experimental Model of Infective Endocarditis

Inhibitex, Inc., Alpharetta, Georgia,¹ Division of Infectious Diseases, Research & Education Institute, Harbor-UCLA Medical Center, Torrance,² UCLA School of Medicine, Los Angeles, California³

Received 28 October 2002/ Returned for modification 5 May 2003/ Accepted 15 July 2003

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 of Staphylococcus aureus and 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-resistant S. 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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