TY - JOUR T1 - Plasmid-Mediated Transmission of KPC-2 Carbapenemase in Enterobacteriaceae in Critically Ill Patients AU - Schweizer, Christian AU - Bischoff, Peter AU - Bender, Jennifer AU - Kola, Axel AU - Gastmeier, Petra AU - Hummel, Manfred AU - Klefisch, Frank-Rainer AU - Schoenrath, Felix AU - Frühauf, Andre AU - Pfeifer, Yvonne AB - Carbapenem-resistant Enterobacteriaceae (CRE) cause health care-associated infections worldwide, and they are of severe concern due to limited treatment options. We report an outbreak of KPC-2-producing CRE that was caused by horizontal transmission of a promiscuous plasmid across different genera of bacteria and hospitals in Germany. Eleven isolates (8 Citrobacter freundii, 2 Klebsiella oxytoca, and 1 Escherichia coli) were obtained from seven critically ill patients during the six months of the outbreak in 2016. One patient developed a CRE infection while the other six patients were CRE-colonized. Three patients died in the course of the hospital stay. Six of the seven patients carried the same C. freundii clone; one K. oxytoca clone was found in two patients, and one patient carried E. coli and C. freundii. Molecular analysis confirmed the presence of a conjugative, blaKPC-2-carrying 70 kb-IncN plasmid in C. freundii and E. coli and an 80 kb-IncN plasmid in K. oxytoca. All transconjugants harbored either the 70 or 80 kb plasmid with blaKPC-2, embedded within transposon variant Tn4401g. Whole genome sequencing and downstream bioinformatics analyses of all plasmid sequences showed an almost perfect match when compared to a blaKPC-2-carrying plasmid of a large outbreak in another German hospital two years earlier. Differences in plasmid sizes and open reading frames point to the presence of inserted mobile genetic elements. There are few outbreak reports worldwide on the transmission of blaKPC-2-carrying plasmids across different bacterial genera. Our data suggest a regional and supraregional spread of blaKPC-2-carrying IncN-plasmids harboring the Tn4401g isoform in Germany. KW - multidrug-resistance KW - Citrobacter freundii ST98 KW - Klebsiella oxytoca ST29 KW - Escherichia coli ST369 KW - IncN KW - WGS KW - 610 Medizin und Gesundheit PY - 2019 LA - eng PB - Robert Koch-Institut JO - Frontiers in Microbiology VL - February 2019 IS - 10 SP - 1 EP - 8 DO - 10.3389/fmicb.2019.00276 ER -