Hospital outbreak of carbapenem-resistant Enterobacterales associated with a blaOXA-48 plasmid carried mostly by Escherichia coli ST399

Abstract

A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous bla_OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

Keywords: E. coli; OXA-48; carbapenem resistance; conjugation rate; enterobacterales; plasmid.

Fig. 1.

Progression of the bla _OXA-48 outbreak, the main bacterial isolates and MLST types involved are highlighted in different colours: E. coli ST399 in dark blue, all other E. coli types in light blue, Klebsiella pneumoniae in yellow, Enterobacter Cloacae in red and Citrobacter koseri in green.

Fig. 2.

Phylogenetic analysis of the pOXA-48 plasmids. (a) Phylogenetic tree of all the pOXA-48 sequences estimated with PhyML under the GTR model (b) Clonal genealogy estimated by ClonalFrameML.

Fig. 3.

Genomic distribution of polymorphisms. On the x axis the plasmid length, the coding regions are highlighted by shaded areas and the plasmid annotation is given on the top. On the y axis the isolates where the polymorphisms are found. The polymorphisms found in the present dataset are shown by red dots while the ones characterising pOXA-48 are given by black lines. When more than one polymorphism is present in a restricted region the number is given next to the symbol. For details of the polymorphisms characterising pOXA-48 see text and Table 1. * Group one plasmids: cpe53, cpe42, cpe07, cpe14, cpe45, cpe19. * Group two plasmids: cpe44, cpe48, cpe54, cpe55, cpe07, cpe32, cpe14, cpe23, cpe18, cpe30, cpe56, cpe04, cpe15, cpe45, cpe40, cpe16.