Evert den Drijver

27 AmpC beta-lactamases: epidemiology, infection control and treatment that promoter/attenuator mutations in E. coli can be confirmed and the presence of the different plasmid families can be examined. Moreover, whole genome sequencing allows is that cluster analysis can be performed and outbreaks can be confirmed based on the combination of this cluster analysis and epidemiological data (Quainoo et al. 2017). However, the reconstruction of full plasmid sequences may necessitate the utilization of multiple sequencing methods, resulting in a time-consuming and labour-intensive analysis. Screening with specific media for AmpC producing Enterobacterales, a common method for other resistance presences such as ESBL, is currently still limited. Although there are producers of media that contain elevated cephamycin concentrations, the number of comparative studies on the effectiveness is limited. The use of a specific antibiotic enrichment broth as a screening strategy has not yet been standardized. The lack of guidelines on screening strategies makes the diversity of screening methods in prevalence studies wide, which influences their heterogeneity. When interpreting prevalence data, it is therefore important to take into account the possible differences in screening methods. Epidemiology of plasmid encoded AmpC in the Netherlands Within the Netherlands, various studies have been conducted into the prevalence of plasmid encoded AmpC producing Enterobacterales (see Table 2). Most studies have focused on rectal or perineal carriage in humans. In general, the prevalence of AmpC producing Enterobacterales rectal carriage in the Netherlands is considered low. In the general population, the prevalence of plasmid AmpC producing E. coli varies between 0.2% and 1.3% (E. Ascelijn Reuland et al. 2015; Van Hoek et al. 2015; van den Bunt et al. 2017). In the two studies of carrier status in hospital patients within the Netherlands, the prevalence was not significantly higher (0.7% to 0.9%) (E. Den Drijver et al. 2018; X. Zhou et al. 2017). Few studies have looked at trends over time. A 2013-2016 study did not find a significant increase in plasmid levels AmpC producing E. coli (E. Den Drijver et al. 2018). Prevalence studies of plasmid AmpC-producing Enterobacterales in clinical isolates, for example from blood cultures, are scarcely performed in the Netherlands. Voets et al. stated that in a collection of isolates from urine cultures and blood cultures with 3rd generation cephalosporin resistance, plasmid AmpC was the cause of the resistance in 5% of E. coli and 4% of K. pneumoniae (Voets et al. 2013). More recent prevalence data of plasmidal AmpC-producing Enterobacterales in clinical isolates are absent in the Netherlands. Outside of the Netherlands, the prevalence of plasmid encoded AmpC producing Enterobacterales is significantly higher (Rodríguez-Guerrero et al. 2022). 2

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