Abstract
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 Enterobacterales 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 blaNDM–1 was found to be present in 35 isolates of which seven additionally carried the carbapenemase gene blaKPC–2. Core genome MLST (cgMLST) revealed different clusters of closely related isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Morganella morganii or Enterobacter cloacae indicating clonal spread. The detailed reconstruction of the plasmid sequences revealed that in all outbreak-associated isolates blaNDM–1 was located on similar composite transposons, which were also very similar to Tn125 previously described for Acinetobacter baumannii. In contrast to Tn125, these structures were flanked by IS26 elements, which could facilitate horizontal gene transfer. Moreover, the identical plasmid was found to be shared by E. coli and M. morganii 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.
Highlights
The rapid spread of antimicrobial resistance (AMR) in nosocomial pathogens poses an urgent threat to patients and public health worldwide
As confirmed by the NRC, carbapenem resistance was mediated by the metallo-β-lactamase New Delhi metallo-β-lactamase-1 (NDM-1)
We found only minor structural variations of the IS26-flanked Tn125 composite transposon among our blaNDM-1 carrying IncA/C and IncN plasmids (IncA/C2 and IncN) that might indicate that these transposons were exchanged across different plasmids
Summary
The rapid spread of antimicrobial resistance (AMR) in nosocomial pathogens poses an urgent threat to patients and public health worldwide. The increasing incidence of multidrug-resistant (MDR) Gram-negative bacteria that are resistant to fluoroquinolones, third-generation cephalosporins, and carbapenems is of major concern, as these MDR pathogens dramatically limit therapeutic options (Pfeifer et al, 2010; Ruppe et al, 2015; Vasoo et al, 2015). For this reason, bacterial pathogens such as Acinetobacter baumanii, Pseudomonas aeruginosa, and various Enterobacterales species have been identified by the World Health Organization as first priority for research and development of new antibiotics (Tacconelli and Magrini, 2016). The administration of carbapenems in antimicrobial chemotherapy supported the selection of specific β-lactamases (carbapenemases) that can hydrolyze virtually all β-lactams, including carbapenems, and often resist prominent β-lactam/β-lactamase inhibitor combinations (Queenan and Bush, 2007; Rodriguez-Bano et al, 2018)
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