Research into the gut microbiome has revealed the widespread influence that microbial species have on their host. Host genetics and environmental factors influence the abundance and diversity of the bacterial species living within the gastrointestinal tract. When the normal composition of the gut microbiota is altered, a dysbiotic state incurs. Inflammatory bowel disease (IBD) is a chronic/relapsing inflammatory disorder of the intestinal mucosa, which is characterized by a state of dysbiosis. Despite the large amount of information studying the role dysbiosis has in the pathogenesis of IBD, it is not clear how the altered microbial composition of the gut in IBD patients leads to susceptibility to enteric pathogens such as Clostridium difficile. This study aims to highlight the features of the gastrointestinal tract that are modified as a result of dysbiosis in the IBD population, and how these features facilitate colonization by C. difficile and symptom development. Review of the available literature demonstrated that the depletion of Clostridial cluster XIVa in IBD-associated dysbiosis alters bile acid metabolism and butyrate fermentation in the colon, ultimately promoting germination of C. difficile spores and weakening the gut's immune response against toxin-mediated inflammation. From continued research into the gut microbiota, more will be understood of how these microbial organisms influence human health and disease.

My original contribution to knowledge is the emergence of an inductively derived conceptual framework that provides a generic account of the way in which people construct and communicate risk. Within this framework, a detailed contextual understanding of how this was applied to C.difficile is developed. Furthermore, in seeking to place responses to health risks in the wider social, cultural and political context, moving beyond a standard critique of media output, an understanding of both how and why the media report health-related risks helped identify ways in which the media can influence how people can construct and communicate about risks. The incidence and severity of C.difficile infection is increasing and it is one of the most common healthcare associated infections, posing a global threat to public health. With the occurrence of major outbreaks within the UK and elsewhere, fear, confusion and unsafe infection prevention and control practices continue to exist among the public and healthcare professionals. Consequently, C.difficile is of particular interest to the media, being the focus of much media reporting. How the public perceive and respond to a health-related risk is shaped by a range of socially and contextually structured evaluations and interpretations, based on a range of factors such as availability heuristics, direct and indirect experiences and social influences, particularly those emanating from the media. Expert risk perceptions and responses on the other hand, are sometimes supposed to be more veridical than those of the public because they are based on calculations of scientific probabilities. Risk perceptions and responses however are context dependent and therefore to be understood, need to be considered within the context that they are perceived and experienced. There is currently little risk perception empirical research to draw upon within the context of C.difficile. The aim of this study was to explore risk perceptions and responses of the public and healthcare professionals within the context of C.difficile and to examine the role of the media in health-related risk reporting. This qualitative study adopted three approaches to data collection: a media coverage analysis of a major C.difficile outbreak, focus groups with the public and healthcare professionals in two geographical areas (an outbreak versus a non-outbreak area), and in-depth, semi-structured interviews with media professionals. The media coverage analysis found that the media portrayed key individuals involved in the outbreak as victims, villains and heroes. These ‘characters’ evolved as the outbreak progressed and new information became available. Such representations were frequently used as a backdrop for the public and healthcare professionals in order to support or refute their perceptions about C.difficile. For the public and healthcare professionals, the consequence of C.difficile and why it occurred was much more salient than estimations of the probability or likelihood of it occurring. Conceptual factors that were found to be important in influencing perceptions included: feelings of vulnerability; attribution of responsibility; judgements about competence; and evaluations of risk communicators. Media professionals were seen as important risk communicators in the focus groups, however they saw themselves as predominantly story tellers and entertainers, rather than ‘educators’. They also believed themselves to be advocates for the public whereby they uncover information that officialdom would seek to keep hidden. What emerged from this study was a coherent, structured and generic account of how various stakeholders construct and communicate about risk. Within this conceptual structuring, a detailed contextual understanding of how this was applied by the public and healthcare professionals around C.difficile was gained. Findings indicate that uncertainty, fear and confusion about C.difficile exist that appear to be influenced by a range of contextual factors such as indirect and direct experiences, social interaction and the media. If risk management and communication strategies are to influence the desired and effective responses towards C.difficile and wider health-related risks, those responsible for managing and communicating risk must consider already established risk perceptions in addition to the factors that have influenced such risk perceptions.

Clostridium difficile (C. difficile) is a gram positive, anaerobic, spore forming bacterium. C. difficile infections are triggered by dysbiosis of the intestinal microbiome linked to age, immune status, and medication; particularly use of antibiotics and proton pump inhibitors (PPI). The spore forming nature of the bacteria gives it the ability to persist in the environment for long periods of time and makes it impervious to many commonly-used hospital cleaning and disinfection products. C. difficile, along with Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) are some of the leading multi-drug resistant hospital acquired infections in the United States. Environmental contamination and patient susceptibility are hypothesized as major contributors to infection transmission in a healthcare setting. We conducted a cross-sectional pilot study aimed at determining the bioaerosol concentration of C. difficile present in the toilet plume of C. difficile infected patients’ rooms. Patient rooms within the University of Iowa Hospital and Clinics (UIHC) were sampled using a customized bioaerosol air impactor device. Environmental samples were collected before and after flushing the toilet to determine the pre-flush and post-flush levels of aerosolized bacteria. Particle density was collected during both pre and post-flush sampling. Activity levels in the rooms were recorded as a potential confounding variable. A total of 144 environmental samples were collected in 24 rooms. Clostridium difficile was detected in two of the twenty-four rooms (8%). There was a 12% (9/72) positive culture rate pre-flush compared to 23% (19/72) post-flush. Wilcoxon rank sum tests revealed a significant increase in particle concentration at the 5.0µm and 10.0µm size between rooms that produced a bacterial culture compared to rooms that did not (p-values 0.0095 and 0.0082 respectively). There was no significant association between the amount of activity in the room and detectable bioaerosol production (p-value=0.605). Next, we performed a randomized control trial of hospital privacy curtains with antimicrobial properties to determine their ability to resist pathogenic bacterial contamination in an intensive care unit setting. Rooms within the surgical and neurological intensive care unit at UIHC were randomized to receive impregnated curtains, impregnated curtains plus Fuzion hypochlorite spray, or standard control curtains. MRSA, VRE, Pseudomonas spp. and Acinetobacter spp. were the four most frequently cultured pathogenic species. Time to event (contamination) analysis identified a significant difference in time to pathogenic contamination between the control curtains and the impregnated curtains post spray (p-value<0.001). The impregnated curtains post Fuzion spray also grew significantly less colonies of bacteria compared to the control curtains (p-value<0.001). After evaluating environmental risk factors that contribute to Clostridium difficile infection, patient related risk factors for infection were evaluated. Proton pump inhibitors are a class of gastric acid reducers that work by reducing the amount of hydrogen ions produced in the stomach. Recent evidence suggests that prolonged use could negatively affect the intestinal microbiome making it more susceptible to enteric pathogens. A nested case control study was done to determine the association between PPI medication duration and C. difficile infection. Fecal microbiome diversity was analyzed via logistic regression in relation to the development of Clostridium difficile infection. A co-morbidity score was created to adjust for other microbiome altering conditions. PPI duration remained a significant predictor of infection after adjusting for the microbiome influence (p-value=0.0123). Environmental contamination remains a significant risk factor for the transmission of hospital acquired infections including C. difficile. Toilets flushing has been shown to produce pathogenic bioaerosols in the healthcare setting. Hospital privacy curtains have been shown to routinely be contaminated with pathogenic bacteria including other gastrointestinal bacteria that could increase susceptibility to C. difficile infection. PPI medication, which is frequently prescribed in the hospital, has been shown to increase the risk of C. difficile infection, although specific microbiome changes could not be identified.

In the United States, influenza causes approximately 36,000 deaths and over 200,000 hospitalizations each year with elderly most often affected. Clostridium difficile infection (CDI) is another major health care challenge and pressing public health issue associated with 14,000 deaths and over 335,000 hospitalizations annually. The use of antibiotics has been implicated in the development of CDI. This study's purpose was to test the relationship of seasonal influenza incidence and antiviral/antibiotic use in CDI development among hospitalized patients. Grounded in the epidemiologic wheel model of man-environment interactions, this retrospective observational study described and analyzed data from a proprietary, laboratory, and pharmacy-based system from a cohort of hospitals. The association between 147 patients with a diagnosis and/or positive test for influenza, the independent variables of delivery of antivirals/antibiotics (n = 130) during the patient's hospitalization, and the dependent variable of positive test or diagnosis of CDI (n = 17) was tested using multiple logistic regressions. The study results did not prove to be significant for the 3 research questions, suggesting no impact of antiviral use (R2 = .05, p = .336), antibiotic use (R2 = .05, p = .290), or antiviral and/or antibiotic use (R2 = .04, p = .382) on development of CDI within 60 days of discharge. However, findings indicated that recommended antiviral medication was inconsistently administered to influenza positive patients and that inappropriate prescribing patterns for antimicrobial agents coincided with seasonal influenza. Implications for positive social change include confirming the importance of antibiotic stewardship as an essential aspect of quality healthcare.

Excess inpatient length of stay (LOS) varies between hospitals and is burdensome to patients and the overall healthcare system. Variation in LOS has often been associated with hospital-level factors, such as hospital efficiency and quality. Clostridium difficile infection (CDI) is an increasingly common hospital-acquired (HA) infection. This thesis explores the connection between hospital incidence of CDI and excess LOS in patients without a CDI. It is hypothesized that HA-CDI incidence may act as a "proxy variable" to capture unobserved hospital characteristics, such as hospital quality or efficiency, associated with prolonged LOS. In addition, hospitals with longer LOS may tend to observe more HA-CDI cases prior to discharge. This thesis analyzes the ability of CDI incidence to capture excess LOS variation across hospitals, while controlling for CDI cases that occur after discharge. We use data on hospital inpatient visits, spanning the years 2005-2011, from three data sources distributed by the Healthcare Cost and Utilization Project: the Nationwide Inpatient Sample (NIS), and the State Inpatient Databases (SID) for California and New York. The NIS provides discharge records from a nationwide sampling of hospitals in a given year. The SIDs are longitudinal populations of inpatient records in each state, and patient records can be linked across stays. We compute a variety of different measures of hospital CDI incidence and identify HA-CDI cases that occur after a patient is discharged. Various multivariable regression models are analyzed to predict LOS at an individual patient level. A generalized linear modeling approach is used, and different distributions and link functions are compared using the Akaike information criterion. A multilevel modeling approach is also used to estimate the amount of between-hospital variation in LOS that can be explained by HA-CDI incidence. We find CDI incidence to be a strong predictive factor for explaining a patient's LOS and is one of the strongest predictive variables we identified. Moreover, CDI incidence appears to primarily capture between-hospital variation in excess LOS. Although we find evidence that present-on-admission indicators may underreport cases of HA CDI, our findings suggest the connection between CDI incidence and excess LOS is driven primarily by CDI cases that are HA. In addition, when we account for HA-CDI cases that occur post-discharge, the relationship between CDI incidence and LOS appears even stronger. Our results suggest that CDI incidence may be a powerful tool for making comparisons of excess LOS across hospitals.

Abstract not available

Background Clostridium difficile is a Gram-positive bacteria found in the large bowel or colon that causes mild to severe intestinal conditions and sometimes death. The primary risk factors for development of Clostridium difficile infection (CDI) include healthcare exposure and recent antimicrobial use. The purpose of this study is to compare risk factors associated with CDI occurring in the Community to those associated with Healthcare Facility Associated CDI in the metro Atlanta population from September 1, 2009 – April 30, 2011. Methods Patients were identified through C. difficile surveillance program of the Georgia Emerging Infections Program (EIP). Prospective, population based, laboratory based surveillance for all positive C. difficile cases in the Georgia Health District 3 (HD3). Due to the sampling scheme, for this analysis CO-HCFA and HCFO cases were combined to make a Healthcare Facility Associated (HCFA) classification. Using SAS, a logistic regression analysis was performed to compare the associated risks between CA and HCFA classifications. Results The rate of CDI in the HD3 counties in Georgia is 84 per 100,000. The median age of infection is 63 and the age range in this study is 1 to 102 years old. CA cases represented 38% of the sampled population. CDI cases 65 and older were more likely to have a Healthcare association compared to CA-CDI cases (p Conclusion This study supports literature about CDI and antimicrobial use and looks further in to the role underlying conditions play as a risk factor for HCFA-CDI cases.

Clostridium difficile is a common and potentially fatal cause of antibiotic-associated diarrhoea and pseudomembranous colitis worldwide. It has been isolated from patients and their surroundings, in healthcare facilities and from the community. C. difficile is able to survive for many months on inanimate surfaces in the form of spores. PCR ribotyping is used in the UK to characterise and identify strain diversity. Investigating how the most problematic strains respond to cleaning regimes may influence the control of disease. This work used the University Hospitals of Leicester Trust as a case study for this purpose of understanding the epidemiology of this pathogen within healthcare facilities. Five individual agar media were compared based on their abilities to recover and resuscitate damaged ribotype 027 spores, a strain associated with disease outbreaks and increased severity. Controlled laboratory experiments with a sub-lethal dose of a germicide were conducted before C. difficile recovery from hospital wards. An additional two sampling campaigns acquired environmental strains. C. difficile isolation after routine cleaning demonstrated the inefficiency of the current recovery regime as C. difficile spores were recovered using direct contact plates, enrichment broths, and resuscitation media. This study used layering of non-selective agar over selective agar, identifying a potential link in the proportions of media following the use of sponges in environmental sampling. All strains were characterised by ribotyping; ribotype 027 was isolated from all sampling cohorts. A four-month epidemiological study was conducted into the ribotype prevalence and distribution from C. difficile-positive faecal specimens. A second survey investigated these effects with a modification of C. difficile detection from faecal samples. Hydrogen peroxide vapour is currently being explored as a means of decontamination of healthcare-associated infections. Inactivation kinetics of ribotype 027 spores were analysed in response to vapour and liquid exposure of hydrogen peroxide. No reports thus far have explored such kinetics and controlled decontamination with both clinical and non-clinical strains. Evidence strongly suggests spores can be inactivated with its application. Furthermore, this study revealed there appears to be significant differences in susceptibility and inactivation of different C. difficile ribotypes.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 5 uppsatser.