17 General introduction use of antibiotics or antiseptics. Homoplasy is a biological phenomenon characterized by the independent occurrence or recurrence of similar traits or genetic changes in different organisms or lineages, irrespective of their genetic relatedness (Wake, Wake, and Specht 2011). It refers to the parallel evolution of similar features, mutations, or genetic variations across diverse populations. This phenomenon poses challenges in determining the true origin or evolutionary history of a particular trait or mutation, as it can arise through convergent evolution rather than through shared ancestry. Is AmpC-mediated resistance a significant concern? Antibiotic resistance resulting from the production of broad-spectrum beta-lactamases in Gram-negative bacteria presents a formidable challenge in both clinical and community settings (Murray et al. 2022). The global dissemination of ESBL-producing variants of E. coli has severely restricted treatment options, and the emergence of AmpC betalactamases is also causing a notable impact, albeit to a lesser extent, by compromising the effectiveness of broad-spectrum penicillins and third-generation cephalosporins. The resistance exhibited by AmpC beta-lactamases to beta-lactamase inhibitor combinations, such as clavulanic acid and tazobactam is of particular concern. Various hypotheses have been proposed to explain this phenomenon, one of which suggests that an elevation in the plasmid copy number of blaCMY-2 containing plasmids could be a contributing factor (Kurpiel and Hanson 2012). Aims of this thesis The main objectives of this thesis are to delve into various aspects of AmpC-related antimicrobial resistance in Enterobacterales. Firstly, the thesis aims to assess the prevalence of rectal colonization by AmpC-producing Enterobacterales in the Netherlands and identify potential trends in colonization rates over time. Secondly, the thesis seeks to optimize the detection of AmpC genes in E. coli through the use of selective media and phenotypic characterization techniques, such as determining minimal inhibitory concentrations of specific antibiotics. The obtained results contribute to the development of a screening strategy that utilizes the phenotype of E. coli to predict the underlying genotype. 1
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