Study on Development of New Methods in the Treatment of Infection Caused by Intracellular Multiplied Bacteria

由于细菌可以在细胞内生长，特别是巨噬细胞和中性粒细胞等吞噬细胞内的细菌，为了开发新的治疗方法，我们尝试应用脂质体包裹的抗生素(头孢他啶，CAZ)，但本身没有任何治疗效果。作为动物模型，我们用豚鼠接种嗜肺军团菌，从日本首例军团病患者中分离到1株(80-045)血清，在麻醉下经气管接种。致死剂量为10^6CFU/只。用于头孢他啶(CAZ)的抗生素，它在体外对生物体具有最强的活性。抗生素被脂质体包裹，包封率约为30%~40%。用脂质体包裹该抗菌素治疗实验性肺炎。结果表明，在致死性实验性军团菌肺炎模型中，心内注射脂质体CAZ可使30%的动物存活。单独使用CAZ治疗的动物不能存活。脂质体包裹的CAZ在腔内注射时是有效的，但在腹膜内注射是有效的。在实验性感染中，30%的动物存活下来。单独与CAZ一起处理的动物没有一只幸存下来。氨苄西林(ABPC)和米诺环素(Mino)均被包裹。ABPC组的存活率为100%，脂质体包裹的ABPC组的存活率为100%。另一方面，Mino的存活率为20%，脂多体包裹的Mino的存活率为80%。这些结果表明，含有抗生素的脂质体在治疗由细胞内繁衍生物引起的内源性疾病方面可能具有治疗优势。

To develop of the new teatment of the infection due to the bacteria which can grow intracellularly,especially intra-phagocytic cells such as macrophages and meutrophiles,we tried to aply liposome coated antibiotics(ceftazidime,CAZ) which did not show any therapeutic effect by itself.As animal model, we used guinea pigs which was inoculated Legionella pneumophila,serogro up 1 (80-045) which was isolated from the first case of Legionnaires' disease in Japan, by the trans-tracheal inoculation under the anesthesia. Lethal dosis was 10^6CFU/animal of the bacteria challenged. The antibiotic used for the ceftazidime (CAZ) which had the most strong acticity against the organism in vitro. The antibiotic was coated by liposome, and the entrapped rate was about 30 to 40 percent. This anti biotic capsulated with liposome was used the treatment of the experimental pneumonia. The results were as follows;In fatal experimental Legionella pneumonia, 30% of animals treated with intracardiac injection of liposome-entrapped CAZ could survived. No animal treated with CAZ alone could sur vived. Liposome-entrapped CAZ was effecative, when given by intracariac injection, but intraperitoneal injection.In experimental infection, 30% of animals treated with intraperitonal injection of liposo me-entrapped CAZ survived. None of the animals treared with CAZ alone survived. Both ampicillin (ABPC) and minocyclin (MINO) were encapsulated the treatment. The survival rates was in ABPC treatment and 100% in lopsome-incapsulated ABPC. On th other hand, MINO shoused 20% of survival rate and lopsome-encapsulated MINO showed 80%. The results suggest that liposomes containing antibiotics might have a therapeutic advant age in the reatment of ingectious diseases caused by intracellular multiplied organisms.