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

为了开发新的治疗细菌感染的方法，我们尝试应用脂质体包裹抗生素，作为动物模型，我们使用接种嗜肺军团菌的豚鼠，血清型up 1（80-045）是从日本首例军团病患者中分离到的，经麻醉下气管接种分离到的。攻毒细菌的致死剂量为10^6 CFU/动物。头孢他啶（ceftazidime，CAZ）是目前体外抗菌活性最强的抗生素。用脂质体包裹抗生素，包封率为30%~ 40%。用脂质体包裹抗生素，用于治疗实验性肺炎。结果如下：在致死性实验性军团菌肺炎中，心内注射脂质体包埋的CAZ治疗的动物存活率为30%。单用CAZ治疗的动物均不能存活。CAZ脂质体腹腔注射对实验性感染有一定的治疗作用，腹腔注射CAZ脂质体动物存活率为30%。单用CAZ处理的动物无一存活。将氨苄青霉素（ABPC）和米诺环素（MINO）包封于治疗中。ABPC治疗组的生存率为100%，而Lopsome-incapsulated ABPC组的生存率为100%。MINO的存活率为20%，脂质体包裹的MINO的存活率为80%。结果提示，含抗生素脂质体在治疗由细胞内微生物增殖引起的感染性疾病方面可能具有一定的治疗优势。

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.