IN-VIVO ACTIVITIES AND PENETRATION OF THE 2 COMPONENTS OF THE STREPTOGRAMIN RP-59500 IN CARDIAC VEGETATIONS OF EXPERIMENTAL ENDOCARDITIS

We evaluated the in vivo activity and the diffusion of radiolabelled R P 57669 (RPI) and RP 54476 (RPII), the two components of the injectabl e streptogramin RP 59500, alone or in combination, in aortic vegetatio ns from experimental endocarditis in rabbits. RPI and RPII demonstrate d in vitro bacteriostatic and bactericidal synergy against a clinical strain of Staphylococcus aureus resistant to methicillin and susceptib le to erythromycin. In experimental staphylococcal endocarditis, RP 59 500 was as effective as vancomycin and significantly more effective th an RPI (P < 0.01) and RPII (P < 0.05). Autoradiography studies showed different patterns of distribution into cardiac vegetations infected w ith Streptococcus sanguis for [C-14]RPI and [C-14] RPII. [C-14]RPI was homogeneously distributed throughout the vegetations whereas [C-14]RP II showed a decreasing gradient of concentration between the periphery and the core of the vegetation, with an approximately 2:1 ratio. [C-1 4] RPI diffused approximately 2 to 4 times more than [C-14]RPII into t he core of the vegetations. Since the injected ratio of RPI and RPII i s 30:70 in RP 59500, the actual RPI:RPII ratio in the core of the vege tation may range from 0.8 to 1.7, a ratio which remains compatible wit h the in vivo synergism demonstrated between the two components.