Aspirin in Infective Endocarditis Leon Iri Kupferwasser Lac-Harbor UCLA Medical Center Division of Infectious Dieseases 1000 West Carson Street Torrence, CA 00509 310/222-6423 Paper B-48, Session 44-B Infectious endocarditis (IE) is a serious and life-threatening infection of the heart valves. The current incidence is 4-6 cases per 100,000 population per year, with an increase in the elderly population. Despite modern antibiotic and surgical therapies, IE retains an overall mortality of 20-30 percent. Embolic events occur in 20-40 percent of patients, presenting predominantly as strokes. They originate from infected heart valve clots(="vegetations"). Staphylococcus aureus is a common cause of IE, and carries the highest mortality among IE pathogens. The potential role of aspirin (acetylsalicylic acid) as an adjunctive treatment for IE is controversial, i.e. the ability to reduce both the growth of vegetations and the rate of embolic events. This work was done by Leon Iri Kupferwasser, Michael R. Yeaman, Shelly M. Shapiro, Cynthia C. Nast, Darwin T. Cheng and Arnold S. Bayer in the St. John's Cardiovascular Research Center, Harbor UCLA Medical Center, Torrance, California, and Cedars-Sinai Medical Center, Los Angeles. The work was supported by a grant of the German Research Foundation to Leon Iri Kupferwasser. The work is presented at the meeting of the American Society for Microbiology, Atlanta, May 17-21, 1998. IE was induced in rabbits using the experimental catheter-induced model. Animals were challenged intravenously by the injection of Staphylococcus aureus strain. Rabbits were given either no therapy (controls) or 4, 8, or 12 mg/kg/d aspirin for three days, beginning 24 hours after infection. The beginning of the aspirin treatment after the induction of IE reflects the clinical situation. Quantitative cultures of endocardial lesions and of kidney lesions revealed a substantial reduction of the amount of bacteria in infection-associated lesions as well as a decrease of vegetation weight in the 4 and 8 mg/kg aspirin dose regimens vesus controls. In the same aspirin dose regimens histopathological analysis demonstrated a significant decrease of embolic events. Also, daily ultrasound investigations of the heart revealed reduced growth and a lower embolic tendency of endocardial lesions when compared to controls. At the 12 mg/kg/d aspirin dose regimen, no differences were found in an! y of the above parameters vesus controls, suggesting that above certain levels, the beneficial effects of aspirin are abrogated in vivo. The MIC of aspirin against the infection S. aureus strain was significantly above the serum-achievable levels. This finding underscores that the beneficial effects of aspiring are not due to intrinsic microbicidal activity of this agent. In conclusion, these data show a beneficial and dose-dependent effect of aspirin on several important aspects of IE pathogenesis, including growth of vegetations and embolization, as well as microbial proliferation within the vegetations.

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