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.

Salmonella Typhimurium with Eight Tandem Copies of blaNDM-1 on a HI2 Plasmid

“…Among the aforementioned plasmids, only p7926H carried the bla NDM-1 gene, derived from Enterobacter hormaechei subsp. Steigerwaltii , which was isolated from Warsaw, Poland, in 2017 [ 31 ]. However, the genetic context of the bla NDM-1 gene of this plasmid differed from that of pST_HI2_NDM-1.…”

Genome-Based Epidemiologic Analysis of VIM/IMP Carbapenemase-Producing Enterobacter spp., Poland

“…ST89 was represented in RefSeq only by 2 isolates in Germany (1 with GIM-1) and 24 NDM-1–positive isolates in Poland during 2017–2020, which we analyzed in a previous study ( 21 ). Therefore, the phylotree comprised 100 isolates, including 98 from Poland (Appendix Figure 7), and consisted of 2 major lineages, each split then into multiple branches, correlating with the regional distribution of the isolates, regardless of their MBL content.…”

“…Only 7 ST121 genomes were present in RefSeq; the 36 VIM isolates in Poland, including outbreaks V–VI, formed 1 of 2 main lineages together with isolates from Brazil, Uganda, Morocco, Germany, and Poland (NDM) ( 21 ) ( Appendix Figure 8). A total of 51 international ST66 isolates formed 2 lineages; 8 isolates in Poland of the outbreak VII belonged, primarily, to the lineage with isolates from Spain, France, and Germany mainly, whereas 10 outbreak VIII isolates clustered within the second lineage of more global character ( Appendix Figure 9).…”

“…We describe VIM/IMP CPE in Poland, which markedly increased in recent years after a period of rather low prevalence. During 2017–2019, the annual VIM/IMP CPE numbers recorded by the National Reference Centre for Susceptibility Testing (n = 545) were comparable with KPC (n = 686) or OXA-48 (n = 383) producers but far behind NDM organisms (n>6,000 [ https://www.korld.nil.gov.pl ]) ( 12 , 14 , 15 , 21 , 30 ). Among all carbapenemase-producing Enterobacter spp., the organisms with VIM/IMP-like enzymes were the predominant group (59.4%).…”

“…On the contrary, ST89 seems to be a local lineage, having been reported mostly in Poland with various VIMs, OXA-48, or NDM-1 so far. However, its repeated identification with GIM-1 in Germany indicates broader spread in central Europe ( 21 , 31 , 32 ).…”