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Clostridium difficile is a common cause of antibiotic-associated diarrhea and occasionally causes the life-threatening disease pseudomembranous colitis. The pathogenicity of the organism has been attributed to the production of two large exotoxins, toxin A (308,000 daltons) and toxin B (269,000 daltons). Toxin A is a powerful enterotoxin and is generally thought to play the more important role in the pathology of the disease. Toxin B may exert its effect after the initial tissue damage by toxin A. Both toxins cause rounding of mammalian culture cells by disrupting the cytoskeletal system. The similar biological activities and high percentage of sequence homology between the two toxins suggest that they have a similar mechanism of action. I found that purified preparations of both toxins cleave skeletal muscle actin at a single site, producing a 38,000 dalton actin fragment, and that the toxins are capable of autodigestion. The proteolytic activity may be involved in the mechanism of action of the toxins. I also analyzed an aberrant strain of C. difficile which reportedly lacked the gene for toxin B. Such a strain would be very useful for the study of the mechanism of toxin A. I concluded however, that the strain contained the genes for both toxin A and toxin B. The toxin genes and resulting proteins appear, however, to be slightly different from those of other strains. / Master of Science

Background: The traditional model of infection control has failed to stop the spread of emerging infectious diseases such as Clostridium difficile-associated diarrhea (CDAD) in the acute care environment. Ecological models, which rely upon identification of susceptible hosts, offer an alternative to the prevention of deadly outbreaks. Previous epidemiological research has identified a number of risk factors associated with CDAD. Utilization of this body of research by nurses is limited due to methodological issues that introduce bias and confounding, and use of variables that have limited meaning to the practicing clinical nurse. Aim: The aim of this study was to develop an ecological model useful for nurses in predicting the susceptibility of individuals to CDAD during an acute care hospital stay. Method: A case-control study compared 66 cases with CDAD to 66 controls matched for the temporal and spatial risk factors of hospital admission date and geographic nursing care unit within the institution. The two subject groups were compared on variables of age, antibiotic burden, laxative or bowel preparation exposure, nutritional status, gastric acid suppression therapy, enteral feeding exposure, and severity of illness as measured on the Horn Severity of Illness index. All subjects were hospitalized between January 1, 2000 and December 31, 2006. Results: On univariate analysis, age, severity of illness, serum albumin levels, length of exposure, and proton pump inhibitor drug burden were significantly associated with CDAD status. Following multivariate analysis, only severity of illness, length of exposure, and decreased antibiotic drug burden were significantly associated with the development of hospital-acquired CDAD. Conclusions: This study supports the use of an ecological perspective in identifying risk factors and interventions to prevent the future spread of this infectious disease.