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 bacteria. The following experiments investigate the ability of
RP 59500 to prevent experimental
endocarditis due to either of two
erythromycin-susceptible 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 bactericidal in vitro. Rats with
catheter-induced aortic vegetations were given single-dose
antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of
RP 59500 per kg of
body weight or 1 g of
vancomycin. Single-dose
RP 59500 prophylaxis successfully prevented
endocarditis due to both the
erythromycin-susceptible parent strains and their
erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition,
RP 59500 also prevented
infection in animals challenged 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 efficacy of
RP 59500 against both
erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with
erythromycin or
clindamycin, which are the standard macrolidelincosamide-
streptogramin antibiotics used for
endocarditis prophylaxis in humans. An oral form of
RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed.