Lewis, IanMansuri, Alikhan2023-05-172023-05-172023-05-08Mansuri, A. (2023). Clinical epidemiology and precision diagnostics for a regionwide cohort of bloodstream infections (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/116542https://dx.doi.org/10.11575/PRISM/dspace/41385Bloodstream infections (BSIs) pose considerable morbidity for patients including progression to septic shock, a life-compromising disease with 30% mortality rate at 30 days from the onset of infection. During my MSc, I have advanced the idea of Precision Infection Management (PIM) as a novel treatment strategy that accounts for microbial virulence alongside host factors for improving mortality rates from BSIs. To lay the foundation for PIM, I conducted two investigations on a 14-year BSI cohort obtained from the Calgary Health Zone. My first objective was to systematically assess the impact of growing antimicrobial resistance on patient mortality trends. I uncovered increasing resistance rates across multiple first-line drugs, including E. coli resistance for ceftriaxone (binomial test p < 0.05). Despite this, E. coli mortality rates remained remarkably stable through the study period (linear model R2 = 0.2). While encouraging, 30-day mortality rates were worryingly high for some species, trending upwards of 30%, furthering a need for the PIM clinical strategy for reducing burden of disease. To address this, I identified microbial virulence factors that could be tested for in the diagnosis of BSIs. I leveraged a cohort of >600 E. faecium isolates and linked microbial proteomic profiles with patient 30-day mortality using Cox proportional hazard and log-rank tests. I identified arcB_1 expression as being significantly associated with 5035 days decreased survival through a 30-day window (adjusted log rank p = 0.0078). While preliminary, this finding is an exciting proof of principle for PIM and implicates virulence-directed therapy as a feasible and promising new treatment avenue that could reduce 30-day mortality.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Precision MedicineBloodstream InfectionsEpidemiologyEducation--Healthmaster thesis