Multiple secondary outbreaks of NDM-producing Enterobacter hormaechei in the context of endemic NDM-producing Klebsiella pneumoniae.

ABSTRACT

BACKGROUND: Consecutive Polish regions have become endemic for NDM-1-producing Klebsiella pneumoniae ST11, followed by K. pneumoniae ST147. Since 2017 a significant increase in NDM-positive Enterobacter hormaechei cases has been observed. OBJECTIVES: To investigate the origin and character of this increase in NDM-positive E. hormaechei. METHODS: The analysis included 160 NDM-producing Enterobacter cloacae complex isolates, recovered in 2015-20 in 37 centres of 9/16 regions. These were typed by PFGE and MLST, and screened by PCR-mapping for NDM-1-encoding Tn125-like elements. Forty-four isolates were sequenced by MiSeq. Species identification was based on whole-genome average nucleotide identity; clonality and phylogeny were inferred by SNP approaches. The structural plasmid analysis was done for 12 isolates sequenced by MinION. RESULTS: The isolates belonged to 11 STs, predominantly ST89 (65.6%), followed by ST146 (15.6%), ST198 (7.5%) and ST1303 (3.7%), representing different E. hormaechei subspecies. Most of the isolates contained the Tn125A variant of the K. pneumoniae ST11 lineage, and several had Tn125F of the ST147. Individual E. hormaechei genotypes represented various epidemiological situations, from sporadic cases to single-hospital, city and regional outbreaks, including one caused by ST89 organisms with 82 cases in 17 centres. Acquisitions of the Tn125A/Tn125F determinants by the E. hormaechei strains occurred around 10 times and were plasmid-mediated, with a significant plasmid rearrangement in case of Tn125F. CONCLUSIONS: The increase in E. hormaechei NDM-1 cases in Poland is a consequence of the uncontrolled spread of NDM-1-producing K. pneumoniae genotypes. Several E. hormaechei lineages have acquired NDM-encoding plasmids in different locales which started 'secondary' progressive outbreaks.