RP 59500 prophylaxis of experimental endocarditis due to erythromycin-susceptible and -resistant isogenic pairs of viridans group streptococci.

Abstract

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.

• Authors: F L'Hériteau, J M Entenza, F Lacassin, C Leport, M P Glauser, P Moreillon
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 39 Issue 7 Pg. 1425-9 (Jul 1995) ISSN: 0066-4804 [Print] United States
• PMID: 7492079 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Virginiamycin
• quinupristin-dalfopristin
• Erythromycin
• Vancomycin

Topics

• Animals
• Conjugation, Genetic
• Drug Resistance, Microbial
• Endocarditis, Bacterial (blood, prevention & control)
• Erythromycin (pharmacology)
• Female
• Microbial Sensitivity Tests
• Rats
• Rats, Wistar
• Streptococcal Infections
• Streptococcus (drug effects, genetics)
• Vancomycin (blood, therapeutic use)
• Virginiamycin (blood, therapeutic use)