Third generation cephalosporin resistance in clinical non-typhoidal in Germany and emergence of -harbouring pESI plasmids.

Non-typhoidal is an important gastrointestinal pathogen causing a considerable burden of disease. Resistance to third generation cephalosporins poses a serious threat for treatment of severe infections. In this study occurrence, phylogenetic relationship, and mechanisms of third generation cephalosporin resistance were investigated for clinical non-typhoidal isolates in Germany. From 2017 to 2019, we detected 168 unique clinical isolates with phenotypic resistance to third generation cephalosporins in a nation-wide surveillance. Compared to previous years, we observed a significant (=0.0002) and consistent increase in resistant isolates from 0.41 % in 2005 to 1.71 % in 2019. In total, 34 different serovars were identified, most often . Infantis (=41; 24.4 %), . Typhimurium (=27; 16.1 %), . Kentucky (=21; 12.5 %), and . Derby (=17; 10.1 %). Whole genome analyses revealed extended-spectrum β-lactamase (ESBL) genes as main cause for third generation cephalosporin resistance, and most prevalent were (=55), (=25), and (=23). There was no strict correlation between serovar, phylogenetic lineage, and ESBL type but some serovar/ESBL gene combinations were detected frequently, such as and in . Infantis or in . Kentucky. The ESBL genes were mainly located on plasmids, including IncI, IncA/C variants, emerging pESI variants, and a novel harbouring plasmid. We conclude that third generation cephalosporin resistance is on the rise among clinical isolates in Germany, and occurrence in various serovars is most probably due to multiple acquisition events of plasmids.