Browsing by Author "Mansuri, Alikhan"

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    Clinical Epidemiology and Precision Diagnostics for a Regionwide Cohort of Bloodstream Infections
    (2023-05-08) Mansuri, Alikhan; Lewis, Ian; Gregson, Daniel; Prenner, Elmar
    Bloodstream 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.