ST-95(Fosfomycin)の基礎的・臨床的検討

Abstract

複雑性尿路感染症患者22例を対象とし, ST-95の臨床的・基礎的検討を行った.ST-95の複雑性尿路感染症に対する成績は満足するものであり, その中でも留置カテーテル群の有効率(75%)は特記されると考えられた.副作用は, 自他覚的に認められなかった.ST-95の尿中排泄は良好であり, 12時間の累積排泄率は, 88.4%であった.尿中生菌数は, 投与後経時的に減少し12時間後には消失した.尿中細菌の形態変化は, 透過型微分干渉顕微鏡では投与終了時より球形となって溶菌に至っていた.透過電子顕微鏡では細胞壁は金平糖状となり, 細胞質との間に空胞様構造が形成され, 細胞質は不整形となった.plasmolysisがおこり, リボゾーム粒子および核質部が粗になって菌体内部が希薄化した像, あるいは溶菌後細胞内容物が流出したと考えられる細胞壁と細胞質膜の残骸が認められた

Clinical effects of ST-95 (fosfomycin) on infections of the urinary tract were studied on the basis of morphological changes of the urinary bacteria. The subjects were 22 inpatients with complex infections of the urinary tract. ST-95 was dissolved in physiologic saline (2 g/100 ml) and administered intravenously by drip infusion over a 1-hour period twice daily for 5 days. According to the UTI criteria, the treatment was effective in 13 (81%) of the 16 evaluable cases. The present effectiveness in 8 patients with chronic catheterization was 75%. No side effects were observed in any patient. Among the laboratory data, GOT and GPT were slightly increased in 1 patient, but their relations with the treatment were unknown. In one patient (P. vulgaris; MIC: 12.5 micrograms/ml), changes in the urinary ST-95 concentration, viable bacterial count, and morphology of the bacteria were studied after the initial administration. The urinary viable cell count was 1.5 x 10(7) cells/ml before administration, but it was reduced to 1.6 x 10(4) cells/ml at the end of the 1-hour infusion, and decreased progressively thereafter to complete disappearance after 12 hours. Under differential interference microscopy, filamentous debris of bacteria and spherical bacteria with irregular surface were observed from immediately after the end of the administration. By transmission electron microscopy, the cell wall showed a number of projections with formation of vacuolar structures in the space between the cell wall and the irregularly-shaped cytoplasms. In conclusion, the results of administration of ST-95 in complex infections of the urinary tract were satisfactory. The morphological changes of the bacteria suggested that this agent acts at an early stage of cell wall synthesis.