In vitro susceptibility to thrombin-induced platelet microbicidal protein is associated with reduced disease progression and complication rates in experimental Staphylococcus aureus endocarditis: Microbiological, histopathologic, and echocardiographic analyses

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-02, Vol.105 (6), p.746-752
• Main Authors: KUPFERWASSER, Leon Iri, YEAMAN, Michael R, SHAPIRO, Shelley M, NAST, Cynthia C, BAYER, Arnold S
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Aortic Valve Insufficiency - diagnostic imaging; Aortic Valve Insufficiency - etiology; Aortic Valve Insufficiency - microbiology; Bacterial diseases; Bacterial endocarditis, myocarditis and pericarditis. Bacterial diseases of the aorta, limb vessels and lymphatic vessels; Biological and medical sciences; Blood Proteins - pharmacology; Disease Models, Animal; Disease Progression; Drug Resistance, Microbial; Echocardiography; Embolism - etiology; Embolism - pathology; Endocarditis, Bacterial - complications; Endocarditis, Bacterial - diagnosis; Endocarditis, Bacterial - drug therapy; Endocarditis, Bacterial - microbiology; Endocarditis, Bacterial - pathology; Heart Valves - microbiology; Heart Valves - pathology; Human bacterial diseases; Infectious diseases; Kidney - microbiology; Kidney - pathology; Medical sciences; Prognosis; Rabbits; Staphylococcal Infections - complications; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus - drug effects; Staphylococcus aureus - pathogenicity; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - etiology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc0602.103721

Mammalian platelets contain small, cationic, staphylocidal peptides, termed thrombin-induced platelet-microbicidal proteins (tPMPs). Evidence suggests that tPMPs play a key role in host defense against endovascular infections, such as infective endocarditis (IE). In the present study, we evaluated the influence of differences in staphylococcal tPMP-susceptibility profiles in vitro on disease severity in experimental IE. Experimental IE was induced in rabbits with either a tPMP-susceptible or an isogenic tPMP-resistant Staphylococcus aureus strain. Vegetation size, left ventricular fractional shortening, and onset of aortic valvular regurgitation were serially assessed by echocardiography over an 11-day postinfection period. In addition, blood cultures were performed daily. Parameters delineated at autopsy included vegetation weights; bacterial densities in vegetations, myocardium, and kidneys; extent of valvular and perivalvular tissue damage; and renal embolization. The following significant differences were observed in animals infected with the tPMP-susceptible versus the tPMP-resistant S aureus strain: substantially lower bacteremia rates (P=0.02); reduced vegetation growth (P