Cross-border emergence of Escherichia coli producing the carbapenemase NDM-5 in Switzerland and Germany

ABSTRACT

A series of clinical NDM-5-producing E. coli isolates obtained from two surveillance networks of carbapenem-producing Enterobacterales from 2018-2019, namely Switzerland (NARA) and Germany (SurvCARE), were analyzed. The 33 NDM-5-producing E. coli isolates were highly resistant to β-lactams including the novel ß-lactam/ß-lactamase inhibitor combinations (ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam), and remained susceptible to fosfomycin, colistin, and tigecycline. Those isolates were assigned to different sequence types (STs) and indicated a predominance of isolates exhibiting the sequence type (ST) ST167 in Switzerland and in Germany (n=10, phylogenetic group C), followed by ST405 (n=4, phylogenetic group E), ST1284 (n=4, phylogenetic group C) and ST361 (n=4, phylogenetic group C). The bla_NDM-5 gene was predominantly present on an IncF-type plasmid (n=29), and to a lesser extent on the narrow-host range IncX3 plasmid (n=4). Sequence analyses of eight NDM-5 plasmids indicated that NDM-5-encoding F-type plasmids varied in size between 86 to 132 kb. The two IncX3 plasmids pCH8NDM5 and pD12NDM5 were 46 and 45 kb in size, respectively. The highly conserved bla_NDM-5 genetic surrounding structures [ΔISAba125-bla_NDM-5-ble_MBL-trpT-dsbD-IS26] of both the F-type and IncX3 plasmids suggested a common genetic origin. The emergence of the NDM-5 carbapenemase was evidenced in particular for the E. coli ST167 clone, which is a successful epidemic clone, known to be associated to both multi-resistance and virulence traits and is therefore of high public health concern. The occurrence of clonally related NDM-5-producing E. coli isolates in Switzerland and Germany further indicates the international spread of this multidrug-resistant superbug at least throughout Europe.