Genomic Epidemiology of Global Carbapenemase-Producing Enterobacter spp., 2008-2014

Abstract

We performed whole-genome sequencing on 170 clinical carbapenemase-producing Enterobacter spp. isolates collected globally during 2008-2014. The most common carbapenemase was VIM, followed by New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae carbapenemase, oxacillin 48, and IMP. The isolates were of predominantly 2 species (E. xiangfangensis and E. hormaechei subsp. steigerwaltii) and 4 global clones (sequence type [ST] 114, ST93, ST90, and ST78) with different clades within ST114 and ST90. Particular genetic structures surrounding carbapenemase genes were circulating locally in various institutions within the same or between different STs in Greece, Guatemala, Italy, Spain, Serbia, and Vietnam. We found a common NDM genetic structure (NDM-GE-U.S.), previously described on pNDM-U.S. from Klebsiella pneumoniae ATCC BAA-214, in 14 different clones obtained from 6 countries spanning 4 continents. Our study highlights the importance of surveillance programs using whole-genome sequencing in providing insight into the molecular epidemiology of carbapenemase-producing Enterobacter spp.

Keywords: Enterobacter spp.; Enterobacteriaceae; antimicrobial resistance; bacteria; carbapenemases; genomic epidemiology; surveillance.

Figure 1

Phylogenetic tree of the different species and sequence types among 160 Enterobacter cloacae complex isolates identified from Enterobacter spp. isolates collected in the Merck Study for Monitoring Antimicrobial Resistance Trends, 2008–2014, and the AstraZeneca global surveillance program, 2012–2014. The tree is rooted with E. cloacae complex Hoffmann cluster IX (Chavda group R) strain 35,699. A total of 369,123 core single-nucleotide polymorphisms were found; 4,010 were used to draw the tree (after phages and recombination sites were excluded). KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin; ST, sequence type; –, information missing; *, isolate identified in another study. Scale bar indicates nucleotide substitutions per site.

Figure 2

Phylogenetic tree of the different clades among 40 Enterobacter xiangfangensis ST14 isolates identified from Enterobacter spp. isolates collected in the Merck Study for Monitoring Antimicrobial Resistance Trends, 2008–2014, and the AstraZeneca global surveillance program, 2012–2014. The tree is rooted with E. hormaechei subsp. hormaechei isolate ATCC49162. A total of 317,867 core single-nucleotide polymorphisms were found; 27,705 were used to draw the tree (after phages and recombination sites were excluded). The isolates from other studies were negative for carbapenemases. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin; ST, sequence type; –, information missing. Scale bar indicates nucleotide substitutions per site.

Figure 3

Phylogenetic tree of the different clades among 51 Enterobacter hormaechei subsp. steigerwaltii ST90 and ST93 isolates identified from Enterobacter spp. isolates collected in the Merck Study for Monitoring Antimicrobial Resistance Trends, 2008–2014, and the AstraZeneca global surveillance program, 2012–2014. The tree is rooted with E. hormaechei subsp. hormaechei isolate ATCC49162. A total of 317,867 core single-nucleotide polymorphisms were found; 27,705 were used to draw the tree (after phages and recombination sites were excluded). The isolates from other studies were negative for carbapenemases. Clades are grouped by color. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin; ST, sequence type; –, information missing. Scale bar indicates nucleotide substitutions per site.

Figure 4

Phylogenetic tree of the different clades among 39 Enterobacter hormaechei subsp. oharae ST108 isolates identified from Enterobacter spp. isolates collected in the Merck Study for Monitoring Antimicrobial Resistance Trends, 2008–2014, and the AstraZeneca global surveillance program, 2012–2014. The tree was rooted with E. hormaechei subsp. hormaechei isolate ATCC49162. A total of 317,867 core single-nucleotide polymorphisms were found; 27,705 were used to draw the tree (after phages and recombination sites were excluded). The isolates from other studies were negative for carbapenemases. Clades are grouped by color. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin; ST, sequence type; –, information missing. Scale bar indicates nucleotide substitutions per site.