RP 59500 prophylaxis of experimental endocarditis due to erythromycin-susceptible and -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 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.
D000818:Animals; D003227:Conjugation, Genetic; D004352:Drug Resistance, Microbial; D004697:Endocarditis, Bacterial / Q000097:blood / Q000517:prevention & control*; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D008826:Microbial Sensitivity Tests; D051381:Rats; D017208:Rats, Wistar; D013290:Streptococcal Infections; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics; D014640:Vancomycin / Q000097:blood / Q000627:therapeutic use; D014769:Virginiamycin / Q000097:blood / Q000627:therapeutic use*
D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D004917:Erythromycin; D014640:Vancomycin