The Burden of Antimicrobial Resistant Bacteremia in Ontario: A Population-wide Analysis of Attributable Mortality from 110 Pathogen-Antibiotic Combinations.
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BACKGROUND: Reliable information on the burden of antimicrobial resistance (AMR) is necessary to confront the threat of antimicrobial resistance. We sought to examine the association between AMR and mortality across cultured bacterial bloodstream pathogens in the province of Ontario, Canada. METHODS: We used linked microbiology data from 114 hospital, community, and public health laboratories to develop a positive bacterial blood culture episode cohort, between January 2017 and December 2021, for the population of Ontario, Canada (population 14.6 million). Antibiotics tested in >10% of cultures of a pathogen, with resistance 1%-99%, were eligible. We used separate proportional hazards models for each pathogen, to estimate the hazard ratio of 30-day mortality for each eligible antibiotic, adjusting for patient risk factors, and summarized results using mixed-effects meta-analysis. RESULTS: We identified 83,962 bacteremia episodes, due to 30 pathogens, and 110 eligible pathogen-antibiotic combinations. 30-day mortality was 17.1% (14,362/83,962). Unadjusted associations between resistance and 30-day mortality were substantially larger (HR=1.47, 95%CI: 1.32-1.65) than adjusted associations accounting for age, sex, healthcare exposures, comorbidities, and co-resistance (HR=1.10, 95%CI: 1.07-1.16). Associations were larger for antibiotics commonly used for empiric treatment (HR=1.18, 95%CI: 1.10-1.26). CONCLUSIONS: We found that antimicrobial resistance was associated with a 10% relative increase in the risk of mortality among patients with bacteremia, and 1.2 AMR attributable deaths per 100,000 population per year in Ontario, Canada. Comprehensive risk adjustment is necessary for understanding the impact of AMR bacteremia on patient outcomes.
