Acetylsalicylic acid reduces vegetation bacterial density, hematogenous bacterial dissemination, and frequency of embolic events in experimental Staphylococcus aureus endocarditis through antiplatelet and antibacterial effects.
BACKGROUND
Platelets are integral to cardiac vegetations that evolve in infectious endocarditis. It has been postulated that the antiplatelet aggregation effect of aspirin (ASA) might diminish vegetation evolution and embolic rates.


RESULTS
Rabbits with Staphylococcus aureus endocarditis were given either no ASA (controls) or ASA at 4, 8, or 12 mg. kg-1. d-1 IV for 3 days beginning 1 day after infection. Vegetation weights and serial echocardiographic vegetation size, vegetation and kidney bacterial densities, and extent of renal embolization were evaluated. In addition, the effect of ASA on early S aureus adherence to sterile vegetations was assessed. In vitro, bacterial adherence to platelets, fibrin matrices, or fibrin-platelet matrices was quantified with either platelets exposed to ASA or S aureus preexposed to salicylic acid (SAL). ASA at 8 mg. kg-1. d-1 (but not at 4 or 12 mg. kg-1. d-1) was associated with substantial decreases in vegetation weight (P<0.05), echocardiographic vegetation growth (P<0.001), vegetation (P<0.05) and renal bacterial densities and renal embolic lesions (P<0.05) versus controls. Diminished aggregation resulted when platelets were preexposed to ASA or when S aureus was preexposed to SAL (P<0.05). S aureus adherence to sterile vegetations (P<0.05) or to platelets in suspension (P<0.05), fibrin matrices (P<0.05), or fibrin-platelet matrices (P<0.05) was significantly reduced when bacteria were preexposed to SAL.


CONCLUSIONS
ASA reduces several principal indicators of severity and metastatic events in experimental S aureus endocarditis. These benefits involve ASA effects on both the platelet and the microbe.
Kupferwasser
L I
LI
Division of Adult Infectious Diseases, Division of Cardiology (S.M.S.), St. John's Cardiovascular Research Center, Harbor-UCLA Medical Center, Torrance, CA, USA. kupferwasser@humc.edu
Yeaman
M R
MR
Shapiro
S M
SM
Nast
C C
CC
Sullam
P M
PM
Filler
S G
SG
Bayer
A S
AS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004617:Embolism / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus
D000900:Anti-Bacterial Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin