RP-59500 PROPHYLAXIS OF EXPERIMENTAL ENDOCARDITIS DUE TO ERYTHROMYCIN-SUSCEPTIBLE AND ERYTHROMYCIN-RESISTANT ISOGENIC PAIRS OF VIRIDANS GROUP STREPTOCOCCI

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacte ria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-su sceptible streptococcal isolates or their constitutively erythromycin- resistant Tn916 Delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bac tericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacteria l inoculation through a computerized pump system which permitted the s imulation of drug kinetics for humans produced by either 7 mg of RP 59 500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 p rophylaxis successfully prevented endocarditis due to both the erythro mycin-susceptible parent strains and their erythromycin-resistant deri vatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals ch allenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo ef ficacy of RP 59500 against both erythromycin-susceptible and -resistan t streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standa rd macrolide-lincosamide-streptogramin antibiotics used for endocardit is prophylaxis in humans. An oral form of RP 59500 which might advanta geously replace some of the older prophylactic regimens is currently b eing developed.