Abstract
We evaluated the in vivo activity and the diffusion of radiolabelled RP 57669 (RPI) and RP 54476 (RPII), the two components of the injectable streptogramin RP 59500, alone or in combination, in aortic vegetations from experimental endocarditis in rabbits. RPI and RPII demonstrated in vitro bacteriostatic and bactericidal synergy against a clinical strain of Staphylococcus aureus resistant to methicillin and susceptible to erythromycin. In experimental staphylococcal endocarditis, RP 59500 was as effective as vancomycin and significantly more effective than RPI (P < 0.01) and RPII (P < 0.05). Autoradiography studies showed different patterns of distribution into cardiac vegetations infected with Streptococcus sanguis for [14C]RPI and [14C]RPII. [14C]RPI was homogeneously distributed throughout the vegetations whereas [14C]RPII showed a decreasing gradient of concentration between the periphery and the core of the vegetation, with an approximately 2:1 ratio. [14C]RPI diffused approximately 2 to 4 times more than [14C]RPII into the core of the vegetations. Since the injected ratio of RPI and RPII is 30:70 in RP 59500, the actual RPI:RPII ratio in the core of the vegetation may range from 0.8 to 1.7, a ratio which remains compatible with the in vivo synergism demonstrated between the two components.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aldridge K. E., Schiro D. D., Varner L. M. In vitro antistaphylococcal activity and testing of RP 59500, a new streptogramin, by two methods. Antimicrob Agents Chemother. 1992 Apr;36(4):854–855. doi: 10.1128/aac.36.4.854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aumercier M., Bouhallab S., Capmau M. L., Le Goffic F. RP 59500: a proposed mechanism for its bactericidal activity. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):9–14. doi: 10.1093/jac/30.suppl_a.9. [DOI] [PubMed] [Google Scholar]
- Bouanchaud D. H. In-vitro and in-vivo synergic activity and fractional inhibitory concentration (FIC) of the components of a semisynthetic streptogramin, RP 59500. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):95–99. doi: 10.1093/jac/30.suppl_a.95. [DOI] [PubMed] [Google Scholar]
- Chambers H. F. Studies of RP 59500 in vitro and in a rabbit model of aortic valve endocarditis caused by methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):117–122. doi: 10.1093/jac/30.suppl_a.117. [DOI] [PubMed] [Google Scholar]
- Cremieux A. C., Maziere B., Vallois J. M., Ottaviani M., Azancot A., Raffoul H., Bouvet A., Pocidalo J. J., Carbon C. Evaluation of antibiotic diffusion into cardiac vegetations by quantitative autoradiography. J Infect Dis. 1989 May;159(5):938–944. doi: 10.1093/infdis/159.5.938. [DOI] [PubMed] [Google Scholar]
- Cremieux A. C., Vallois J. M., Maziere B., Ottaviani M., Bouvet A., Carbon C., Pocidalo J. J. 3H-spiramycin penetration into fibrin vegetations in an experimental model of streptococcal endocarditis. J Antimicrob Chemother. 1988 Jul;22 (Suppl B):127–133. doi: 10.1093/jac/22.supplement_b.127. [DOI] [PubMed] [Google Scholar]
- Etienne S. D., Montay G., Le Liboux A., Frydman A., Garaud J. J. A phase I, double-blind, placebo-controlled study of the tolerance and pharmacokinetic behaviour of RP 59500. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):123–131. doi: 10.1093/jac/30.suppl_a.123. [DOI] [PubMed] [Google Scholar]
- Fantin B., Carbon C. In vivo antibiotic synergism: contribution of animal models. Antimicrob Agents Chemother. 1992 May;36(5):907–912. doi: 10.1128/aac.36.5.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fantin B., Leclercq R., Arthur M., Duval J., Carbon C. Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium. Antimicrob Agents Chemother. 1991 Aug;35(8):1570–1575. doi: 10.1128/aac.35.8.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leclercq R., Nantas L., Soussy C. J., Duval J. Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):67–75. doi: 10.1093/jac/30.suppl_a.67. [DOI] [PubMed] [Google Scholar]
- Maple P. A., Hamilton-Miller J. M., Brumfitt W. World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus. Lancet. 1989 Mar 11;1(8637):537–540. doi: 10.1016/s0140-6736(89)90076-7. [DOI] [PubMed] [Google Scholar]
- Nougayrede A., Berthaud N., Bouanchaud D. H. Post-antibiotic effects of RP 59500 with Staphylococcus aureus. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):101–106. doi: 10.1093/jac/30.suppl_a.101. [DOI] [PubMed] [Google Scholar]
- Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pechère J. C. In-vitro activity of RP 59500, a semisynthetic streptogramin, against staphylococci and streptococci. J Antimicrob Chemother. 1992 Jul;30 (Suppl A):15–18. doi: 10.1093/jac/30.suppl_a.15. [DOI] [PubMed] [Google Scholar]