Trends in incidence and antimicrobial resistance for five major causes of bacteraemia in a Canadian metropolitan area, 2006-22: a genomic and antimicrobial use cohort study

@misc{pham2026trends,
  title = {{Trends in incidence and antimicrobial resistance for five major causes of bacteraemia in a Canadian metropolitan area, 2006-22: a genomic and antimicrobial use cohort study}},
  author = {T. M. Pham and J. T. Smith and T. D. Mortimer and Y. Grad and A. M. Earl and I. A. Lewis and PRIME Consortium},
  howpublished = {medRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.27.26361471},
  url = {https://www.medrxiv.org/content/10.64898/2026.08.27.26361471v1},
  note = {CC BY-NC},
}

TY  - UNPB
TI  - Trends in incidence and antimicrobial resistance for five major causes of bacteraemia in a Canadian metropolitan area, 2006-22: a genomic and antimicrobial use cohort study
AU  - T. M. Pham
AU  - J. T. Smith
AU  - T. D. Mortimer
AU  - Y. Grad
AU  - A. M. Earl
AU  - I. A. Lewis
AU  - PRIME Consortium
PY  - 2026
DA  - 2026/08/27
PB  - medRxiv
DO  - 10.64898/2026.08.27.26361471
UR  - https://www.medrxiv.org/content/10.64898/2026.08.27.26361471v1
AB  - BackgroundUsing a population-based cohort from the Calgary Health Zone (CHZ), Canada, we integrated longitudinal antimicrobial susceptibility and prescribing data with the whole genome sequences of five major pathogens. We aimed to assess how antimicrobial resistance (AMR) responds to prescribing changes and determine which bacterial strains shape these dynamics.  MethodsWe analysed antibiotic prescribing rates, clinical and genomic data from 7,271 Staphylococcus aureus, 1,609 Enterococcus faecalis, 801 Enterococcus faecium, 11,363 Escherichia coli, and 2,319 Klebsiella pneumoniae isolates, associated with bacteraemia episodes in the CHZ between 2006-2022. Genomic clusters (referred to as strains) were identified using StrainGST and assigned to known sequence types (STs) or clonal complexes (CCs). Strain-level incidence, stratified by community-onset (isolates collected [≤]48h after admission) and hospital-onset (>48h after admission), AMR phenotypes, and prescribing rates were modelled using negative-binomial and binomial regression. Temporal trends were quantified using average annual percentage change (AAPC).  FindingsBetween 2010-2022, fluoroquinolone prescribing declined in both community (AAPC=-6{middle dot}8% [95% CI -8{middle dot}1, -5{middle dot}4]; p<0{middle dot}0001) and hospital settings (AAPC=-5{middle dot}1% [-6{middle dot}5, -3{middle dot}7]; p<0{middle dot}0001). This was accompanied by a significant reduction in fluoroquinolone resistance among Gram-positive species. Specifically, S aureus bacteraemia resistant to clinically important antibiotics, cloxacillin, ciprofloxacin, erythromycin, and clindamycin, declined from 2006 to 2022, mostly in hospital-onset cases (AAPC=-16{middle dot}0%, [-19{middle dot}3%, -12{middle dot}7%], p<0{middle dot}0001). In E coli, ceftriaxone and ciprofloxacin resistance were clustered in ST131 and the emerging ST1193; the latter increased steadily, particularly in community-onset cases (AAPC=17{middle dot}7%, [9{middle dot}0%, 30{middle dot}0%], p<0{middle dot}0001). CTX-M-27-producing E coli ST131 strains increased (AAPC=23{middle dot}8%, [17{middle dot}4%, 30{middle dot}5%], p<0{middle dot}0001) between 2008-2022, while CTX-M-14-producing E coli ST131 declined (AAPC=-15{middle dot}9%, [-21{middle dot}3%, -10{middle dot}2%], p<0{middle dot}0001) between 2013-2022. These trends were paralleled by an increase in community cephalosporin prescribing (AAPC=7{middle dot}3%, [4{middle dot}2%, 10{middle dot}5%], p<0{middle dot}0001) between 2010-2022. For K pneumoniae, hypervirulent ST23 was most common (N=88) with an increasing trend in incidence (AAPC=2{middle dot}3%, [-4{middle dot}4%, 9{middle dot}4%]) between 2006-2019.  ConclusionsThe contrasting resistance trends between Gram-positive and Gram-negative species underscore the complexity of AMR control efforts. Effective strategies will require stewardship efforts targeting multiple drug classes, genomic surveillance for emerging resistant strains, and interventions extending beyond hospital settings.  FundingThis study was funded by a Large Scale Applied Research Project competition award (2017) from Genome Canada, administered via Genome Alberta. IAL is supported by an Alberta Innovates Translational Health Chair and a UCalgary Research Excellence Chair, with additional support from the Canada Foundation for Innovation (CFI-JELF 34986), the Natural Sciences and Engineering Research Council (DG 04547). Microbial isolates were prepared for analysis at the Alberta Centre for Advanced Diagnostics, which is supported by PrairiesCan (000022734). This work was also supported by federal funds from the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grant number U19AI110818 to the Broad Institute. JTS is additionally supported by the NIH/NIAID F32AI179151.  Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published in English up to Dec 23, 2025, using (antibiotic[tiab] OR antimicrobial[tiab]) AND (use[tiab] OR prescribing[tiab] OR consumption[tiab]) AND (resistance[tiab] OR "multidrug resistance"[tiab]) AND (relationship[tiab] OR association[tiab] OR correlation[tiab] OR effect[tiab] OR impact[tiab] OR influence[tiab] OR regression[tiab]) AND (genomic OR genetic OR ""molecular epidemiology) AND ("Staphylococcus aureus" OR "Escherichia coli" OR "Klebsiella pneumoniae" OR "Enterococcus faecalis" OR "Enterococcus faecium") NOT animal. This search yielded 739 articles.  Numerous studies have characterised the molecular epidemiology of these species over the past two decades:  For Staphylococcus aureus, extensive genomic surveillance has revealed that a limited number of sequence types have dominated global infections over the past two to three decades. Pandemic hospital-associated methicillin resistant S aureus (MRSA) strains such as CC5, CC22, CC80, and CC30 were widely established in the 1990s and early 2000s, often carrying large multidrug-resistant staphylococcal cassette chromosome mec (SCCmec) elements. Since then, community-associated MRSA strains, including ST8 (CC8, USA300), ST59, and ST80, have emerged and expanded, frequently harbouring SCCmec IV or V. Livestock-associated MRSA ST398 has also become widespread, particularly in Europe and North America. While vancomycin resistance in S aureus remains rare, reduced susceptibility has been reported sporadically, especially in ST5 and ST8. Overall, the distribution of S aureus sequence types continues to shift regionally, with the spread of community-associated strains into hospitals. These patterns largely reflect data from high-income countries whereas strain distribution tends to be more heterogeneous in low-and middle-income countries.  In Enterococcus faecium, genomic analyses have revealed a split population structure: clade A1 (clonal complex 17) comprises the vast majority of clinical, multidrug-resistant…
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