AUTHOR=Weber Robert E. , Pietsch Michael , Frühauf Andre , Pfeifer Yvonne , Martin Maria , Luft Dirk , Gatermann Sören , Pfennigwerth Niels , Kaase Martin , Werner Guido , Fuchs Stephan 

TITLE=IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02817

DOI=10.3389/fmicb.2019.02817

ISSN=1664-302X

ABSTRACT=<p>One of the most demanding challenges in infection control is the worldwide dissemination of multidrug-resistant (MDR) bacteria in clinical settings. Especially the increasing prevalence of carbapenemase producing Gram-negative pathogens poses an urgent threat to public health, as these enzymes confer resistance to almost all β-lactam antibiotics including carbapenems. In this study, we report a prolonged nosocomial outbreak of various NDM-1-producing <italic>Enterobacterales</italic> species due to clonal spread and cross-species exchange of plasmids and possibly transposons. Between July 2015 and September 2017, a total of 51 carbapenemase-positive isolates were collected from 38 patients and three environmental sources in a single German hospital. Combining molecular typing methods and whole genome sequencing, the metallo-β-lactamase gene <italic>bla</italic><sub>NDM–1</sub> was found to be present in 35 isolates of which seven additionally carried the carbapenemase gene <italic>bla</italic><sub>KPC–2</sub>. Core genome MLST (cgMLST) revealed different clusters of closely related isolates of <italic>Escherichia coli</italic>, <italic>Klebsiella pneumoniae</italic>, <italic>Citrobacter freundii</italic>, <italic>Morganella morganii</italic> or <italic>Enterobacter cloacae</italic> indicating clonal spread. The detailed reconstruction of the plasmid sequences revealed that in all outbreak-associated isolates <italic>bla<sub>NDM–1</sub></italic> was located on similar composite transposons, which were also very similar to Tn<italic>125</italic> previously described for <italic>Acinetobacter baumannii</italic>. In contrast to Tn<italic>125</italic>, these structures were flanked by IS<italic>26</italic> elements, which could facilitate horizontal gene transfer. Moreover, the identical plasmid was found to be shared by <italic>E. coli</italic> and <italic>M. morganii</italic> isolates. Our results highlight the importance of detailed genome-based analyses for complex nosocomial outbreaks, allowing the identification of causal genetic determinants and providing insights into potential mechanisms involved in the dissemination of antibiotic resistances between different bacterial species.</p>