Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis.
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.
Inhibitex, Inc., Alpharetta, Georgia 30004, USA. jvernachio@inhibitex.com
John
J
Vernachio
Arnold S
AS
Bayer
Thuan
T
Le
Yin-Li
YL
Chai
Bradley
B
Prater
Amy
A
Schneider
Brenda
B
Ames
Peter
P
Syribeys
Jeffrey
J
Robbins
Joseph M
JM
Patti
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007136:Immunoglobulins / Q000627:therapeutic use*; D007167:Immunotherapy; D016106:Methicillin Resistance; D009895:Opsonin Proteins / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D007136:Immunoglobulins; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D014640:Vancomycin; D005340:Fibrinogen