The Complex Interplay among Diabetes Mellitus Chronic Kidney Disease and Different Klebsiella pneumoniae Infections in Taiwan

摘要

In the community setting Klebsiella pneumoniae is a potential pathogen with various clinical manifestations including septicemia pneumonia urinary tract infection (UTI) meningitis and purulent abscesses at various sites In particular a distinctive clinical syndrome which is characterized by community-acquired K pneumoniae bacteremia with primary liver abscess has been recognized in Taiwan My PhD research started from National Health Insurance Research Database (NHIRD) to analyze the role of diabetes mellitus (DM) as most important host factor in pyogenic liver abscess (PLA) caused by K pneumoniae The large-scale cohort study confirmed the previously reported link between diabetes and risk of PLA onset This study advanced the knowledge highlighting a stronger association noted for younger patients; and that diabetic patients with underlying biliary tract diseases and liver cirrhosis are at even greater risks of PLA onset and should be the objects of particular attention for the prevention of PLA onset in patients with diabetes Based on the knowledge of our epidemiologic study we found the close association between DM PLA and K pneumoniae To be investigated more deeply I constructed a large population-based type 1 diabetes mellitus (T1DM) cohort in Taiwan diagnosed between 1999 and 2010 The data analyzed in my thesis were derived from Taiwan’s NHIRD that provides a valid and nation-wide registration system for T1DM I investigated the long-term trends of incidence rate of T1DM in all sex and age stratifications and to explore the overall as well as the age and sex-specific risk of mortality in patients with T1DM I also investigated the long-term risk of end stage renal disease (ESRD) in patients with T1DM and examined how age at registration of diabetes time period of registration and sex affect these risks At the same time I enrolled all the K pneumoniae strains at National Cheng Kung University Hospital since 2006 to survey the clinical and microbiological characteristics in UTI abscess and peritoneal dialysis (PD)-related infections First I investigated the expression of hypermucoviscosity (HV) and the presence of the virulence gene of K pneumoniae in UTI strains including the association of host factors especially DM with K pneumoniae associated UTI Second I evaluated the host and bacterial characteristics of K pneumoniae in recurrent UTI (RUTI) The results demonstrated all the RUTI occurred in DM patients Third I studied the change in distribution of causative organisms in PD-related peritonitis during a 22-year period I investigated the microbiological characteristics of K pneumoniae and host factors in PD-related peritonitis such as old age DM or immunocompromised status to predict critical case for clinical therapy Finally I screened a novel adhesion gene KPN_2990 from my uropathogenic K pneumoniae and investigated the role in K pneumoniae UTI by mutant construction with inflammatory cytokines analysis and animal UTI model I concluded that the mechanism of action of KPN_2990 can be explained partially by the modulation of proinflammatory cytokines response to Klebsiella infection Their mode of action is certainly much more complex and further research is necessary for a better understanding of this phenomenon

獎項日期	2015 8月 25
原文	English
監督員	Ming-Cheng Wang (Supervisor)