Novel Enterobacter Lineage as Leading Cause of Nosocomial Outbreak Involving Carbapenemase-Producing Strains

Racha Beyrouthy; Marion Barets; Elodie Marion; Cédric Dananché; Olivier Dauwalder; Frédéric Robin; Lauraine Gauthier; Agnès Jousset; Laurent Dortet, François Guérin; Thomas Bénet; Pierre Cassier; Philippe Vanhems; Richard Bonnet

Disclosures

Emerging Infectious Diseases. 2018;24(8):1505-1515. 

In This Article

Abstract and Introduction

Abstract

We investigated unusual carbapenemase-producing Enterobacter cloacae complex isolates (n = 8) in the novel sequence type (ST) 873, which caused nosocomial infections in 2 hospitals in France. Whole-genome sequence typing showed the 1-year persistence of the epidemic strain, which harbored a bla VIM-4 ST1-IncHI2 plasmid, in 1 health institution and 2 closely related strains harboring bla CTX-M-15 in the other. These isolates formed a new subgroup in the E. hormaechei metacluster, according to their hsp60 sequences and phylogenomic analysis. The average nucleotide identities, specific biochemical properties, and pangenomic and functional investigations of isolates suggested isolates of a novel species that had acquired genes associated with adhesion and mobility. The emergence of this novel Enterobacter phylogenetic lineage within hospitals should be closely monitored because of its ability to persist and spread.

Introduction

Controlling the dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is challenging because carbapenems are among the few antimicrobial drugs that can be used to treat severe infections in this family.[1,2] Tzouvelekis et al. calculated the mortality rate of primary bacteremia involving CPEs without active therapy to be 54%.[3] Thus, CPEs may carry the threat of a return to the pre–antimicrobial drug era.

The Enterobacter cloacae complex (ECC) has become the third most common species among CPEs in France.[4] ECCs are not dominated by any single genotype,[5] and only certain subspecies/species have previously been associated with infections and nosocomial outbreaks.[6–8] The accurate identification of species and subspecies within the ECC is therefore needed to monitor outbreaks and infections.

The identification of species and subspecies within the ECC is challenging, and even more problematic because routine bacterial identification methods based on biochemical tests or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry are yet unable to distinguish between them.[9–13] In a seminal work, Hoffmann and Roggenkamp defined 13 genetic clusters (I –XIII) of the ECC on the basis of hsp60 gene sequences and assigned them to species and subspecies.[14] Recently, Chavda et al. extended the number of clusters in the ECC to 18 phylogenomic groups (A–R) by analyzing core single-nucleotide polymorphisms (SNPs) in 390 whole genomes.[15]

Using whole-genome sequencing (WGS) approaches, we investigated a cluster of nosocomial carbapenemase-producing ECC isolates collected over a 13-month period in a university hospital in France. The results suggest a double-string diffusion mechanism involving the emergence of both a carbapenemase-encoding plasmid and an ECC phylogenetic lineage not previously described.

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