A COMPARISON OF TWO STRAINS OF E COLI TO PRODUCE SEPTIC SHOCK IN DOGS

虽然活细菌通常会引起感染， 细菌毒素与活细菌对抗， 目前尚不清楚，如果细菌毒素是重要因素， 可能需要针对这些毒素。即使没有细菌存活 或生长，这些预先形成的毒素可能在决定发病率方面很重要， and mortality.针对这些毒素的治疗可能很重要 添加到抗生素治疗。 使用两个E。大肠杆菌无毒力E. coli（O86：H8）和强毒E.杆菌 (06：41：K2）在犬模型中，我们设计了一项研究，以确定是否 生物毒力因子或细菌毒素在 导致败血性休克血液动力学休克，血培养， 内毒素水平和存活率在两种生物体活的情况下连续进行， 这两种微生物都被杀死，并从这些微生物中纯化内毒素。 本研究大约进行了4人年。初步结果 来自这些研究的报告已经提交给了美国联合会， 临床研究和重症监护医学会。这些数据 建议的毒力因子比进行的更重要， 内毒素对内毒素血症发展的影响。 为了进一步解决这个问题，我们正在与LCI的Tom Russo合作， NIAID和最近的布法罗大学研究了 内毒素是同一株大肠杆菌的毒力因子。杆菌我们 使用基因破坏技术在E.大肠杆菌菌株， 内毒素O型侧链（另一种毒力因子）缺陷。 这将进一步探讨内毒素在感染性休克中的相对作用。 目前正在做许多工作，以针对这种病原体在人类败血症 冲击.人们对这些数据很感兴趣， 导致感染发病率的因素将指导未来的试验。 治疗儿童和成人感染性休克。

While live bacteria commonly cause infection, the relative role of bacterial toxins versus live bacteria to produce morbidity and mortality is not known, If bacterial toxins are important factors, therapies directed at these toxins may be required. Even if no bacteria remain alive or grow, these preformed toxins may be important in determining morbidity and mortality. Therapies directed at these toxins may be important additions to antibiotic therapy. Using two E. coli nonvirulent E. coli (O86:H8) and a virulent E. coli (06:41 :K2) in the canine model, we designed a study to determine whether organism virulence factors or bacterial toxins were more important in producing septic shock. Measures of hemodynamic shock, blood cultures, endotoxin levels and survival were done serially with both organisms live, both organisms killed, and with purified endotoxin from these organisms. Approximately 4 man years have gone into this study. Preliminary results from these studies have been presented at the American Federation of Clinical Research and the Society of Critical Care Medicine. These data suggested virulence factors are much more important than performed endotoxins on development of endotoxemia. To further address this issue we are collaborating with Tom Russo of LCI, NIAID and more recently the University of Buffalo to examine the role of endotoxin as a virulence factor within the same strain of E. coli. We are using a gene disruption technique to produce in an E. coli strain with a deficiency in endotoxin o type side chains (another virulence factor). This will further explore the relative role of endotoxin in septic shock. Much work is presently being done to target this pathogen in human septic shock. There has been much interest in these data as determination of the factors that produce morbidity in infection will guide trials for future therapies of children and adults with septic shock.