165 Summary and general discussion selective media for AmpC-producing Enterobacterales. In Chapter 5, a comprehensive evaluation is presented, aiming to assess the performance of various agars containing cefotaxime and ceftazidime. This evaluation takes into consideration the specificity and sensitivity of these agars in detecting both chromosomal AmpC-hyperproducing and plasmid AmpC-harbouring Escherichia coli strains, in comparison to ESBL-producing E. coli and those without ESBL, pAmpC, or cAmpC hyperproduction. Furthermore, the impact of incorporating cefoxitin into these agars is examined to improve the detection of both chromosomal AmpC-hyperproducing and plasmid AmpC-harbouring E. coli strains. The addition of cefoxitin showed little influence on sensitivity but increased the specificity of AmpC-producing E. coli detection. However, the agar used did not differentiate between plasmid-encoded and chromosomal AmpC-producing E. coli strains. It is worth noting that the screening set primarily consisted of blaCMY-typecontaining and chromosomal AmpC-producing E. coli strains, which warrants further studies to evaluate an agar containing cefotaxime or ceftazidime with cefoxitin in a clinical setting. Nevertheless, the screening agars are expected to be feasible for AmpC rectal carriage screening when employing a pre-enrichment step, similar to current ESBL screening agar strategies (M. F.Q. Kluytmans-Van Den Bergh et al. 2015). Sources and transmission routes of AmpC-mediated resistance Understanding the sources and transmission routes of antimicrobial resistance vectors is crucial to prevent further increases in antibiotic resistance. Plasmids, as mobile genetic elements, play a significant role in the dissemination of antimicrobial resistance genes, harbouring various resistance mechanisms. The prevalent AmpC resistance gene, blaCMY2, is frequently linked to specific plasmid families, such as IncA/C, IncB/O/K, and IncI. In Chapter 6, the focus is on exploring the relationship between blaCMY-2-containing IncI1-pST12 plasmids in epidemiologically linked and unrelated Enterobacteriaceae isolates from both humans and livestock. The objective was to assess the feasibility of accurately distinguishing between related and unrelated samples based solely on plasmid sequencing data. By investigating this relationship, valuable insights can be gained into the potential transmission dynamics and relatedness of antimicrobial resistance strains. Although the study was conducted using a limited sample size, the findings clearly demonstrate the similarity of plasmid sequences, as indicated by the low number of single nucleotide polymorphism (SNP) differences and a high number of shared 9
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