162 Chapter 9 Introduction This thesis aims to investigate various aspects of AmpC-mediated antimicrobial resistance in Enterobacterales, with a particular focus on Escherichia coli. The first objective was to determine the prevalence of rectal colonization by AmpC-producing Enterobacterales in the Netherlands and analyse any potential trends in colonization rates over time. Another key aim was to optimize the detection of ampC genes in E. coli through the use of selective media and phenotypic characterization techniques. Additionally, this thesis examined the feasibility of accurately distinguishing related samples with AmpC-producing E. coli from unrelated ones based solely on plasmid sequencing data. Furthermore, it explored whether mutations occurring in the ampC promoter/attenuator region of E. coli are homoplastic and whether these homoplastic mutations are associated with cefotaxime resistance. Finally, the association between plasmid presence and the level of resistance to specific antibiotics was investigated. This involved comparing the sequencing depth between chromosomal household genes and plasmid-encoded scaffolds containing the blaCMY-2 gene, while also utilizing the ratio as an estimated plasmid copy number. This thesis concludes with a comprehensive summary and discussion that synthesizes the main findings from the conducted studies and places them in a broader perspective. Prevalence of AmpC-producing Enterobacterales in the Netherlands The increasing global burden of antimicrobial resistance poses a significant and escalating threat. ESBL-producing Enterobacterales, in particular, show alarming upward trends worldwide, as evidenced by a tenfold increase in the global intestinal carriage rate of ESBL E. coli in the community, as reported in a recent review by Bezabih et al. (Bezabih et al. 2022). Despite relatively low prevalence in Western European countries, including the Netherlands (E. A. Reuland et al. 2016), the rise in global mobility has facilitated the spread of antimicrobial-resistant bacteria through travel (Paltansing et al. 2013; Lorme et al. 2018; Hu, Matsui, and W. Riley 2020; Raffelsberger et al. 2023). However, it is important to note that traveling is not the sole risk factor associated with the carriage of resistant Enterobacterales. A recent study by Meijs et al. has revealed an elevated prevalence of ESBL and plasmid-encoded AmpC producing E. coli and K. pneumoniae among Dutch veterinary healthcare workers when compared to the general
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