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Title:The acquisition of clostridium difficile-associated disease: the role of nutritional care
Author(s):Peters, Vanessa A.
Director of Research:Erdman, John W.
Doctoral Committee Chair(s):Fahey, George C.
Doctoral Committee Member(s):Teran-Garcia, Margarita; Nakamura, Manabu T.
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Clostridium difficile
Clostridium difficile-associated disease
C. difficile
Abstract:In 2013, the Centers for Disease Control and Prevention (CDC) classified Clostridium difficile, the bacterium responsible for Clostridium difficile-associated disease (CDAD), as one of the three most threatening microorganisms to human health. C. difficile has outpaced methicillin-resistant Staphylococcus aureus as the most common healthcare pathogen, and is currently the leading cause of antibiotic-associated diarrhea and gastroenteritis-related deaths in the United States. Advances in research, national campaigns for healthcare safety, mandated disease reporting, legislation for hospital accountability, and the creation of new antibiotics have all proven ineffective. The current treatment standards, which have been utilized since the discovery of C. difficile pathogenesis in pseudomembranous colitis in the 1970’s, have shown waning effectiveness and may actually increase disease recurrence and treatment failure. Interest in non-antibiotic alternatives, the evolving understanding of the microbiome as a critical defense against pathogens, and the efficacy of oral nutrition supplements in hospitalized populations with gastrointestinal disease suggest that targeted nutritional therapy may provide a clinical benefit. The intestinal microbiota can be modified by diet, and is critical for immunity, metabolism, synthesis of vitamins and other bioactive substances, and resistance against pathogens; the microbiota prevents pathogen adherence directly through physical competition, and indirectly through the proliferation of anti-inflammatory and antibiotic-like substances. Any event that disturbs the microbiome may allow opportunistic pathogens, like C. difficile, to adhere, colonize, and produce disease. Therefore, the ability to protect or reestablish the microbiota could have vast therapeutic implications. Preliminary data suggest that nutritional status may relate directly to CDAD susceptibility. CDAD patients show markedly reduced gastrointestinal microbial diversity, which may promote pathological colonization and disease recurrence. Possible methods of repopulating the GI tract with healthful bacteria include fecal microbiota transplants and the administration of probiotics or prebiotics. The recent popularity of fecal transplants for treatment of GI infections is promising, but the process is expensive, unregulated, and aesthetically unappealing. Similarly, the ingestion of probiotics has generally shown potential in patients with recurrent CDAD, but premature degradation in the upper GI tract can be problematic, and caution is advised for use in critically ill or immunocompromised patients. Although prebiotics have the unique advantage of being well-tolerated, stable, commercially available, and easily incorporated into the diet, clinical studies in this area have been diverse, small, and scarce. Improvements in human studies have been attributed to measurable elevations in butyrate, an anti-inflammatory short-chain fatty acid byproduct of prebiotic fermentation, as well as an attenuated pro-inflammatory cytokine response. The first aim of this research was to summarize the existing clinical literature regarding prebiotic administration and CDAD with a systematic review. The systematic review search identified five studies, yet only three were suitable for inclusion in a meta-analysis. Studies were heterogenous, but appeared to slightly, though not significantly, favor prebiotics, as 35/374 (9.36%) supplemented patients experienced CDAD compared to 64/393 (16.28%) patients in the control groups (OR 0.43, P=0.05). Neither side effects nor mortality differed between treatments, and further research is needed to determine whether prebiotics may provide a clinical benefit for either current or potential CDAD patients. We next evaluated medical records from Carle Foundation Hospital (CFH) in two separate time periods to identify risk factors for CDAD and to determine whether malnutrition was related to CDAD prevalence and patient outcomes. A month-long preliminary study identified six risk factors (advanced age, admission from another healthcare unit or facility, recent hospitalization, and a history of diarrhea or documented CDAD diagnosis within the previous year) correlated with CDAD prevalence. These risk factors were then used to separate 1,277 patients from 2014, and then 973 patients from 2016, into high-risk groups for primary studies. Initial analysis revealed that advanced age, previous diarrhea, previous CDAD, malnutrition, nutrition consultation requests, and admission from a healthcare facility were individually associated with CDAD diagnosis in both 2014 and 2016. However, when multiple regression analysis was used to identify predictor variables for CDAD, only previous CDAD (OR 111.49, P<0.0001), age ≥65 years (OR 0.43, P=0.004), nutrition consultation requests (OR 1.70, P=0.04), and BMI (OR 0.96, P=0.02) retained significance in 2014, and only previous CDAD (OR 52.95, P<0.0001) and nutrition consultation requests (OR 1.96, P=0.004) in 2016. Although malnutrition was not independently associated with CDAD, we believe that it may more accurately mirror critical overlooked factors, such as frailty or comorbidity. CDAD prevalence did not change between 2014 and 2016 (18.6% vs 17.7%, P=0.57), although both malnutrition (10.4% vs 14.7%, P=0.002) and mortality (14.9% vs 18.9%, P=0.01) increased within the same time period. While our retrospective studies showed many consistencies between the two years and appeared to successfully identify high-risk patients within our sample, data restrictions prevented assessment of disease severity. Both the prevalence of malnutrition and CDAD were unusually low in comparison with national averages for hospitalized patients. Although the exclusive use of a high-risk group prevents comparison with current literature, we intend to use the results of these projects to better direct interventions to prevent CDAD in at-risk individuals, and thereby mitigate bacterial transmission and lessen the overall CDAD disease burden.
Issue Date:2018-07-10
Rights Information:Copyright 2018 Vanessa A. Peters
Date Available in IDEALS:2018-09-27
Date Deposited:2018-08

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