Nichterlein T, Kretschmar M, Budeanu C, Bauer J, Linss W, Hof H
Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany.
Antimicrob Agents Chemother. 1994 Jul;38(7):1501-6. doi: 10.1128/AAC.38.7.1501.
Bay Y 3118 is a new quinolone derivative with pronounced activity against gram-positive bacteria including the facultatively intracellular bacterium Listeria monocytogenes. Bay Y 3118 was tested in vitro and in animal models of listeriosis. All strains of L. monocytogenes and other Listeria spp. were highly susceptible in vitro; the MICs for these organisms ranged from 0.062 to 0.25 micrograms/ml. Bay Y 3118 was rapidly bactericidal in vitro, with a postantibiotic effect occurring for 3 h after removal of the antibiotic. L. monocytogenes was eliminated from infected L929 cells treated with Bay Y 3118, suggesting a bactericidal effect on the listeriae in these cells. Immunocompetent mice were rapidly cured by treatment with 4 mg every 12 h. Concomitantly, the levels of interleukin 6 and gamma interferon in mouse sera declined rapidly. In immunocompetent mice, treatment with 2 mg of Bay Y 3118 every 12 h resulted in a greater initial reduction in the listerial counts in the organs than treatment with 2 mg of ampicillin every 12 h. Bay Y 3118 completely eliminated L. monocytogenes from the livers and spleens of chronically infected nude mice. However, some of the bacteria reappeared after the cessation of therapy. In conclusion, Bay Y 3118 is an excellent candidate substance for the therapy of infections caused by facultatively intracellular gram-positive bacteria such as L. monocytogenes.
Bay Y 3118是一种新型喹诺酮衍生物,对革兰氏阳性菌具有显著活性,包括兼性胞内菌单核细胞增生李斯特菌。对Bay Y 3118进行了体外和李斯特菌病动物模型试验。所有单核细胞增生李斯特菌菌株和其他李斯特菌属在体外均高度敏感;这些菌株的最低抑菌浓度范围为0.062至0.25微克/毫升。Bay Y 3118在体外具有快速杀菌作用,去除抗生素后有3小时的抗生素后效应。用Bay Y 3118处理的感染L929细胞中的单核细胞增生李斯特菌被清除,表明对这些细胞中的李斯特菌有杀菌作用。免疫功能正常的小鼠每12小时用4毫克治疗可迅速治愈。同时,小鼠血清中白细胞介素6和γ干扰素水平迅速下降。在免疫功能正常的小鼠中,每12小时用2毫克Bay Y 3118治疗比每12小时用2毫克氨苄西林治疗导致器官中李斯特菌数量的初始减少更大。Bay Y 3118完全清除了慢性感染的裸鼠肝脏和脾脏中的单核细胞增生李斯特菌。然而,治疗停止后一些细菌重新出现。总之,Bay Y 3118是治疗由兼性胞内革兰氏阳性菌如单核细胞增生李斯特菌引起的感染的优秀候选物质。