Clostridium difficile infection: hospital-based epidemiology in Tainan and establishment of an animal model

  • 洪 元斌

Student thesis: Doctoral Thesis


Clostridium difficile is a major cause of nosocomial antibiotic-associated diarrhea and has increasing incidence and fatality rates The incidence of C difficile infection (CDI) in Taiwan is unclear C difficile colonization is an independent risk factor for C difficile-associated diarrhea However the impact of C difficile colonization in hospitalized patients is not known Gaps in our understanding of the pathogenesis of CDI present major challenges to the development of better preventive and therapeutic strategies against this problem C difficile toxins breach the intestinal barrier and trigger musical inflammation and intestinal damage In addition to the effects of bacterial toxins impaired host immunity is also associated with increased risks of CDI suggesting that the pathogenesis of CDI needs to be further characterized The receptor-mediated mechanisms by which macrophages recognize and phagocytize bacteria including clostridia have not been well analyzed Toll-like receptors (TLRs) are the major components of innate immunity The relationship between TLRs and CDI was analyzed in this work An epidemiological study was performed in the medical wards of a regional hospital Fecal culture and toxin ELISA tests were performed for C difficile colonization in all hospitalized patients; during hospitalization these patients were followed up for the development of CDI All clinical C difficile isolates were further characterized by toxinotyping and ribotyping C difficile colonization was noted to cause a higher risk of CDI Prior exposure to proton pump inhibitors or antimicrobial agents was a risk factor for C difficile colonization and infection During the study period some hypervirulent C difficile strains such as ribotype 126 and 027 were discovered in Tainan Patients with a specific TLR polymorphism had a higher risk of C difficile colonization and infection than those without the polymorphism To analyze the pathophysiology of CDI a mouse model of CDI was designed to investigate the predisposing role of PPI in CDI Mice developed severe CDI after PPI use The mouse model of CDI could be used to analyze the contribution of innate immunity in CDI To investigate the role of TLRs in the pathogenesis of CDI Tlr2-/- or Tlr4-/- mice were infected by C difficile The mice then were examined for changes in the severity in clostridial colitis Colon pathology findings in C difficile-infected wild mice and Tlr2-/- or Tlr4-/- mice were compared Tlr-/- mice presented more severe CDI than wild mice indicative of a protective role of TLRs in CDI The first epidemiological information of C difficile colonization and infection rates in Taiwan were obtained in the described clinical studies In addition basic research findings increased our understanding of TLRs and how they mediate the inflammatory responses against CDI By combining these results translational studies will likely draw the attention of medical professionals who deal with CDI Furthermore the described CDI mouse model can be utilized to develop preventive or therapeutic strategies for combating CDI
Date of Award2015 Aug 19
Original languageEnglish
SupervisorWen-Chien Ko (Supervisor) & Pei-Jane Tsai (Supervisor)

Cite this