15 General introduction Various types of plasmid-encoded ampC genes have been identified, with blaCMY-2 (beta-lactamase type CMY-2) being the most common in the Netherlands (E. Ascelijn Reuland et al. 2015; E. Den Drijver et al. 2018). These genes vary in their hydrolysing capability and are associated with specific bacterial species, such as blaCMY-2 in E. coli and Salmonella spp. and blaDHA in Klebsiella spp (Philippon, Arlet, and Jacoby 2002). Multiple studies have investigated the epidemiology of plasmid-encoded ampC genes in the Netherlands, but information on trends remains limited. Figure 1. Sequence of the E. coli ATCC 25922 ampC promoter/attenuator region. Sequence regions based on Tracz et al. with numbering according to Jaurin et al. and (Jaurin et al. 1981; Tracz et al. 2007). How to detect AmpC beta-lactamases Detection and differentiation of plasmid-encoded AmpC and chromosomal-encoded AmpC genes pose challenges due to their coexistence. This difficulty is amplified in the presence of ESBL. The Dutch guideline for detection of highly-resistant microorganisms recommends initial screening for plasmid AmpC by assessing resistance to cephamycins, using a cefoxitin minimal inhibitory concentrations (MICs) of 8 mg/L or higher and elevated MICs for cefotaxime, ceftriaxone, or ceftazidime (MIC >1 mg/L), as indicators of AmpC production (J.A.J.W Kluytmans et al. 2021). Confirmation tests involve inhibitory tests using cloxacillin or boric acid and various disc diffusion or gradient strip methods that compare zone differences between third-generation cephalosporins with or without an inhibitor. 1
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