Background: C. difficile is one of the primary infectious causes of morbidity and mortality in Canada. Colonized patients can pose a risk to others as a factor in the transmission and development of hospital-associated C. difficile infections. Despite immense efforts and resources invested in the reduction in C. difficile transmission within Canada and Hamilton Health Sciences – further reduction in these rates are unlikely, and novel screening strategies are imperative in this field of study. Methods: This project was a retrospective cohort study of adult in-patients admitted to either The Juravinski, Hamilton General, or St. Joseph’s Healthcare Hamilton Hospitals from January to April 2018 and September 2018 to August 2019. MSRA/VRE swabs were collected during admission or through universal point prevalence screening and subsequently tested for colonization. Results: From the 1056 patients in the data sample, 72 were colonized with asymptomatic C. difficile resulting in a prevalence rate of 6.81%. In-patient point prevalence screening strategies identified more carriers than admission swabs alone (p < 0.001). Risk factors for colonization on admission were being female (OR 2.66, 95% CI 1.02-8.33) and previous CDI (OR 4.76, 95% CI 1.49 – 13.86). During hospitalization, risk factors for colonization were previous CDI (OR 4.75 95% CI 2.14-9.94) and recent hospitalization within the last 12 months (OR 2.35, 95% CI 1.30-4.42). The multi-level Cox PH model identified those with a recent hospitalization (OR 2.21, 95% CI 1.32 – 3.73) and those with previous CDI (OR 2.40, 1.34 – 4.30) were twice as likely to develop asymptomatic C. difficile colonization throughout hospitalization. Conclusion: The addition of universal point prevalence screening in addition to admission screening helped identify more than double the amount of carriers in the population. Moreover, a previous hospitalization, previous CDI, and being female may indicate patients at the highest risk of colonization. / Thesis / Master of Science (MSc) / C. difficile infection (CDI) is a severe infectious disease. Patients with asymptomatic C. difficile present a risk to others as they can contribute to the spread and development of hospital-associated CDI. We are currently unsure of the proportion of adult in-patients colonized with asymptomatic C. difficile. Identifying these carriers early on in their hospital stay is imperative to reduce CDI rates in health care settings. Our study objectives were to determine the best screening strategies to identify asymptomatic carriers, identify risk factors for carriage, and understand the transition from asymptomatic C. difficile to symptomatic CDI. We demonstrated that being female, being recently hospitalized or previously having CDI may increase a patient's risk of being an asymptomatic carrier. Also, timely screening throughout a hospital stay in addition to admission screening helped identify more colonized in-patients. Lastly, we determined that 1 in 5 carriers would go on to develop symptomatic CDI infection.

Clostridium difficile is an important nosocomial pathogen and the leading cause of antibiotic-associated diarrhea. In the early 2000's, major outbreaks of C. difficile occurred in the Canada and the United States, both caused by the same strain, the North American Pulsed-Field type 1 (NAP1). Recently a steady rise in prevalence of a NAP4 strain was observed. This study utilized phenotypic and genotypic methods, including whole genome sequencing, to fully characterize and better understand the emergence of NAP4 in Canada. Through WGS it was revealed that an emerging NAP4 PFGE type (PFGE type 0033) has acquired a novel phage (phiCD505), which harbors transcriptional regulators and is inserted in close proximity to a GMP synthase gene. The role of these phage encoded transcriptional regulators on C. difficile virulence factors and/or disruption of normal expression of GMP synthase remain to be elucidated, but might be contributing to the emergence of this PFGE type. / October 2016

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1990. / Vita. Abstract. Includes bibliographical references. Also available via the Internet.

Thesis (Ph.D.)--University of Western Australia, 2003.

The main purpose of this study was to assess outcomes (i.e., inpatient mortality, transplant failure or rejection, colectomy, and hospital length of stay) of clostridium difficile infection (CDI) and the association of expenditures (i.e., charges and costs) and CDI in pediatric solid organ transplant (SOT) recipients. Data from the 2000, 2003, 2006, and 2009 Kids’ Inpatient Database (KID) files were used to identify events with SOT- related ICD-9-CM diagnosis codes. Logistic regression was used to assess the association of CDI and dichotomous outcome variables, while log-linked gamma regression models were used to assess the association of CDI and continuous outcome variables. Methods accounting for the complex survey sample design of the KID were used when performing all statistical analyses. The total number of pediatric SOT hospital events was 48,286. The overall prevalence of CDI for pediatric SOT hospitalizations was 1.76%. For SOT hospitalizations with CDI, inpatient mortality was 1.63%; the prevalence of transplant failure or rejection events was 27.71%; the prevalence of a colectomy was 4.86%. The median hospital length of stay was seven days; the median charge and cost for each hospitalization was $48,409 and $17,412, respectively. The results showed that CDI was not significantly associated with inpatient mortality or transplant failure/ rejection in pediatric SOT hospitalizations. SOT patients with CDI were 2.6 times more likely to have a colectomy than SOT patient without CDI. The mean hospital length of stay (LOS) for a SOT admission with CDI was approximately 2 times the mean LOS for a SOT admission without CDI. The mean charges and the mean costs for a SOT admission with CDI was approximately 2 times that for a SOT admission without CDI. In conclusion, CDI diagnoses were not significantly associated with higher inpatient mortality or transplant failure/ rejection for pediatric SOT hospitalizations. But CDI was significantly associated with a higher prevalence of a colectomy, longer hospital LOS, higher charges, and higher costs (all p<0.05). To avoid substantially higher expenditures and health care utilization, CDI in pediatric SOT recipients should be prevented when possible and promptly diagnosed and treated when it occurs. / text

Clostridium difficile infection (CDI) has recently emerged as a major health problem. An understanding of the micro-epidemiology of the infection is decisive for the design and implementation of control polices. Presently, typing using PCR ribotyping (RT), Multi-locus Sequence Typing (MLST) and Multi-locus Variable Number Tandem Repeat Analysis (MLVA) can be used to investigate recent transmission events of C. difficile. In the case of MLVA, different criteria have been used to classify strains and this reflects inconsistencies in the contemporary knowledge of change in MLVA polymorphisms. In this study, temporal and spatial investigations were conducted to better understand the dynamics of change in C. difficile VNTR loci. The 164 isolates from the collection yielded 25 different STs, with ST161 and ST171 being newly described. The congruence of MLST to the other typing methods of RT and tcdC, strengthens the robustness of discrimination of these methods. Sub-typing using MLVA, however yielded 139 strains, and again there was congruence to the aforementioned methods. Clustering of MLVA strains into groups revealed Single and Multi-Isolate Strains linked together as single locus variants with groups coordinating with MLST types within ST1 and ST3. The lowest MLVA diversity was seen in the Period of Increased Incidence and was primarily responsible for high incidence rates. These groups of MLVA related isolates were used to characterise the instability of the repeat sequences of MLVA loci. 2 Locus differences were examined from the perspective of the genetic role of the locus, DNA polymerase amplification, the impact of different growth conditions on the fitness of the repeat sequences and of the frequency of repeat changes in the natural population. These studies have focused on the on the drivers of change of VNTR loci in general and will allow a more rational approach to using MLVA loci in epidemiological studies.

published_or_final_version / Microbiology / Master / Master of Medical Sciences

Backgroud: Clostridium difficile infection (CDI) is a global concern since the emergence of the hyper-virulent strain NAP1/BI/027. The incidence of CDI has been increasing and active surveillance of Clostridium difficile epidemiology is of paramount importance. In studying the epidemiology of CDI, PCR ribotyping is a very useful method in finding the genetic relatedness of outbreak and epidemic strains. Characterisation of Clostridium difficile isolates can help surveillance and active monitoring, hence reducing the chance of potential outbreaks. Aim: The aims of this study is to investigate the epidemiology of Clostridium difficile in Hong Kong in the year 2010, and that of a Clostridium difficile outbreak in 2011 by using capillary gel electrophoresis-based PCR ribotyping. Results: Among the 307 toxigenic isolates, 139 isolates (45.3%) were characterized as existing ribotypes. Ribotype 012 was the predominant ribotype (17.3%), followed by ribotype 002/0 (15.6%). A total of 144 isolates (46.9%) were characterized as new ribotypes. The remaining 24 isolates (7.8%) were characterized as of high resemblance of existing ribotypes. A total of 8/12 isolates (66.7%) of the outbreak strains were found to be ribotype 002/0. Conclusion: The predominant strains of Clostridium difficile in 2010 was ribotype 012. The 2011 outbreak in Kowloon Hospital was an outbreak of Clostridium difficile ribotype 002/0. Capillary gel electrophoresis-based PCR ribotyping was showed to be a useful tool in investigation of Clostridium difficile outbreaks and study of Clostridium difficile epidemiology. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

Introduction: Clostridium difficile infection (CDI) is the major bacterial agent causing hospital-acquired diarrhea. The incidence and severity of CDI has increased significantly in recent decades. The distribution of PCR ribotype varies among the countries. PCR ribotype 017 and 002 are the predominant ribotypes in China and Hong Kong respectively. Molecular characterization of C. difficile isolates is useful for outbreak investigation and surveillance. Both PCR ribotyping and Multilocus variable-number tandem-repeat analysis (MLVA) are reliable molecular tools for characterization of C. difficile from outbreak and sporadic case. MLVA allows subtyping of genetically related C. difficile isolates of the same ribotype by their distinctive MLVA patterns. The aim of this study was to characterize the outbreak and sporadic C. difficile isolates of PCR ribotype 002 and 017 by using capillary gel electrophoresis-based PCR ribotyping and MLVA. Their cytotoxicity, sporulation rate and germination efficiency were also investigated in the study. Results: A total of the 26 C. difficile isolates were identified by PCR ribotyping including fifteen isolates of PCR ribotype 002, eight isolates of ribotype 017, and three isolates of other ribotypes. The isolates of the same ribotypes were further sub-typed into outbreak and sporadic cluster. All isolates showed toxin-producing capability. The sporualtion rates of outbreak isolates of PCR ribotype 002 were significantly higher than that of sporadic isolates of PCR ribotype 002. Statistically higher sporulation rate was also observed in the outbreak isolates of PCR ribotype 017. The germination rate was also statistically higher in the outbreak isolates of PCR ribotype 002 than the sporadic cases. Conclusion: Capillary electrophoresis-based PCR ribotyping identified fifteen C. difficile PCR ribotype 002 and eight PCR ribotype 017 in this study. MLVA then refined these isolates into two corresponding sub-groups of outbreak and sporadic isolates. Higher sporulation and germination rates were observed in the outbreak isolates. Sporadic isolates demonstrated relatively lower sporulation and germination rates. The current evidences correlate the genotypic characterization to sporulation activity and germination efficiency. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

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