Nichterlein T, Kretschmar M, Hof H
Institute of Medical Microbiology and Hygiene, University of Heidelberg, 68135 Mannheim, Germany.
J Chemother. 1996 Apr;8(2):107-12. doi: 10.1179/joc.1996.8.2.107.
RP 59500 (Synercid) a streptogramin derivative, is a mixture of two water-soluble substances, RP 57669 (quinupristin), and RP 54476 (dalfopristin). It was tested in vitro and in vivo against Listeria strains. All strains were sensitive in vitro. The MICs of 60 strains of Listeria monocytogenes, L. seeligeri, L. ivanovii, and L. innocua were between 0.156 and 0.625 mg/l. Strains of L. grayi were inhibited by 1.25 mg/l of RP 59500. In contrast to its bactericidal effect against other gram-positive bacteria, RP 59500 was bacteriostatic against L. monocytogenes in all concentrations tested (up to 16 x MIC). However, it exerted a pronounced postantibiotic effect. RP 59500 was ineffective against intracellular L. monocytogenes multiplying in L929 mouse fibroblast cells. When it was included in the supernatant of the cells in nontoxic concentrations of below 12.5mg/l alone or in combination with gentamicin (50mg/l) it was not able to inhibit the growth of the listeriae in the cells. However, when tested in peritoneal exudate cells, it was bacteriostatic against L. monocytogenes. In spite of its relatively poor effects on listeriae in vitro, RP 59500 was as active as erythromycin in a mouse model of listeriosis. When mice iv infected with L. monocytogenes were treated ip with 2mg/animal every 12 hours with either erythromycin or RP 59500, both substances prevented growth of the bacteria in the organs, but were unable to eradicate the listeriae. We conclude that RP 59500 is a candidate substance for the treatment of human listeriosis which might be used when therapy with ampicillin is not feasible.
RP 59500（司帕沙星）是一种链阳性菌素衍生物，是两种水溶性物质RP 57669（奎奴普丁）和RP 54476（达福普汀）的混合物。对其进行了针对李斯特菌菌株的体外和体内测试。所有菌株在体外均敏感。60株单核细胞增生李斯特菌、斯氏李斯特菌、伊氏李斯特菌和无害李斯特菌的最低抑菌浓度在0.156至0.625毫克/升之间。格氏李斯特菌菌株被1.25毫克/升的RP 59500抑制。与它对其他革兰氏阳性菌的杀菌作用不同，RP 59500在所有测试浓度（高达16倍最低抑菌浓度）下对单核细胞增生李斯特菌均具有抑菌作用。然而，它具有明显的抗生素后效应。RP 59500对在L929小鼠成纤维细胞中繁殖的细胞内单核细胞增生李斯特菌无效。当以低于12.5毫克/升的无毒浓度单独或与庆大霉素（50毫克/升）联合包含在细胞上清液中时，它无法抑制细胞内李斯特菌的生长。然而，在腹膜渗出细胞中进行测试时，它对单核细胞增生李斯特菌具有抑菌作用。尽管RP 59500在体外对李斯特菌的作用相对较差，但在李斯特菌病的小鼠模型中它与红霉素的活性相当。当用单核细胞增生李斯特菌静脉感染的小鼠每12小时腹腔注射2毫克/动物的红霉素或RP 59500时，两种物质均能阻止细菌在器官中的生长，但无法根除李斯特菌。我们得出结论，RP 59500是治疗人类李斯特菌病的候选物质，在氨苄西林治疗不可行时可能会被使用。
