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

Discussion

One major issue regarding CPEs is whether the main driver of the spread of carbapenemases is the transmission of successful clonal lineages or the horizontal transfer of carbapenemase genes by mobile genetic elements such as plasmids. Our study provides evidence for the spread of an epidemic VIM-4–encoding IncHI2 plasmid in distinct lineages of the ECC and the 1-year persistence of an epidemic strain ST-873, suggesting a double-string diffusion mechanism involving the emergence of both a VIM-4–encoding plasmid and a persistent ECC phylogenetic lineage.

ECC accounted for 9.4% and VIM-4–producing ECC for 3.9% of CPEs during 2015 in France.[27] Only 1 additional case of a VIM-4–producing ECC was observed in Paris during the same period, and only 16 VIM-4–producing Enterobacteriaceae cases were diagnosed: the 7 ECC cases included in this study, 6 cases of E. coli in the Paris area, and 2 cases of Citrobacter freundii in the north of France. During this period, 6 other cases of CPE were identified in the same hospital: 5 produced oxacillinase 48 carbapenemases, and 1 produced New Delhi metallo-β-lactamase 1; these cases, in line with common observations in France and other countries in Europe, were imported.[4] Our investigation was therefore prompted by the contrast between the low incidence of VIM-4–producing ECC cases in France and our case series, which suggested a new carbapenemase-spreading factor.

All the VIM-4 isolates we found harbored a similar blaVIM-4–encoding, self-conjugative plasmid. The blaVIM-4 gene has previously been reported only in IncA/C plasmids in a neighboring country (Italy).[28] The epidemic plasmid we identified belongs to the ST1-IncHI2 incompatibility group. IncHI2 plasmids are frequent among the ECCs and are often associated with the dissemination of genes encoding extended-spectrum β-lactamases and, at least to some extent, blaVIM-1.[29] Although bla VIM-4 differs from bla VIM-1 by a point mutation, the IncHI2 bla VIM-4 plasmids we identified substantially diverge from previously reported bla VIM-1 plasmids by the ≈50kb region encoding the associated resistance genes.

The VIM-4 epidemic strain ST873 persisted in the hospital for ≈1 year despite the application of specific isolation precautions for patients colonized or infected. During the investigation of another nosocomial outbreak that occurred in 2016 in Caen University Hospital (692 km from Lyon), we identified 2 CTX-M-15–encoding ECC strains belonging to ST873, which suggests that the spread of ST873 is not geographically limited. These strains had traits of speciation and specific genes related to signal transduction, cell motility, and adhesion. These functions have a crucial role in the initiation of biofilm formation,[30] which was enhanced in the ST873 isolates compared with the other VIM-4 isolates in our study. Biofilm formation, a key function for host–pathogen interactions and environmental survival, may explain the successful persistence of ST873 isolates in the hospital settings of this study.

Nosocomial infections mediated by Enterobacteriaceae can be transmitted to patients in medical settings by HCWs, patient-to-patient spread, or environmental sources.[31] Our findings emphasize the need to consider clinical circumstances such as bed contamination, as previously observed.[32] In addition, the VIM-4֪–encoding plasmid pECC-VIM4 transferred to a bacterial recipient at room temperature, which could explain why successful horizontal transfer into ECC multiclonal isolates occurred in the hospital environment and provided support for the crucial importance of environmental reservoirs in the transmission of nosocomial pathogens. Hence, the threat of outbreaks can be limited by high-quality cleaning and disinfection of patient-care areas and the regular replacement of equipment such as mattress covers.

In conclusion, we report a nosocomial outbreak of multiclonal VIM-4–producing ECC that originated from contamination in the hospital environment. The predominant clone belongs to a new lineage in the ECC and should be closely monitored in the context of nosocomial infections caused by its apparent ability to maintain and spread in a hospital setting. Our study also delineated the multifactorial spread of the VIM-4 carbapenemase and emphasizes the usefulness of ECC phylogenomic typing in the investigation of outbreaks.

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