Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.744431
Keywords
Citrobacter; Carbapenemase; Germany; WGS; IncN-plasmid; MLST; ARGs
Categories
Funding
- Bundesministerium fuer Bildung und Forschung (BMBF, Germany) within the German Center for Infection Research (DZIF) [8032808811, 8032808818, 8032808820]
- Hessian State Ministry for Social Affairs and Integration (HMSI) within the project SurvCARE Hessen
- Hessian Ministry of Higher Education, Research and Arts within the project HuKKH (Hessisches universitaeres Kompetenzzentrum Krankenhaushygiene)
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The rise of Carbapenem-resistant Enterobacterales (CRE) is a growing threat to patient safety and healthcare systems worldwide. Citrobacter species are increasingly being identified as clinical multidrug-resistant pathogens, with carbapenemase groups such as KPC, OXA-48/-like, and MBL (VIM, NDM) detected. These carbapenemase genes are predominantly located on plasmids, highlighting the potential risk of dissemination in hospital settings.
The rise of Carbapenem-resistant Enterobacterales (CRE) represents an increasing threat to patient safety and healthcare systems worldwide. Citrobacter spp., long considered not to be a classical nosocomial pathogen, in contrast to Klebsiella pneumoniae and Escherichia coli, is fast gaining importance as a clinical multidrug-resistant pathogen. We analyzed the genomes of 512 isolates of 21 CRE species obtained from 61 hospitals within a three-year-period and found that Citrobacter spp. (C. freundii, C. portucalensis, C. europaeus, C. koseri and C. braakii) were increasingly detected (n=56) within the study period. The carbapenemase-groups detected in Citrobacter spp. were KPC, OXA-48/-like and MBL (VIM, NDM) accounting for 42%, 31% and 27% respectively, which is comparable to those of K. pneumoniae in the same study. They accounted for 10%, 17% and 14% of all carbapenemase-producing CRE detected in 2017, 2018 and 2019, respectively. The carbapenemase genes were almost exclusively located on plasmids. The high genomic diversity of C. freundii is represented by 22 ST-types. KPC-2 was the predominantly detected carbapenemase (n=19) and was located in 95% of cases on a highly-conserved multiple-drug-resistance-gene-carrying pMLST15 IncN plasmid. KPC-3 was rarely detected and was confined to a clonal outbreak of C. freundii ST18. OXA-48 carbapenemases were located on plasmids of the IncL/M (pOXA-48) type. About 50% of VIM-1 was located on different IncN plasmids (pMLST7, pMLST5). These results underline the increasing importance of the Citrobacter species as emerging carriers of carbapenemases and therefore as potential disseminators of Carbapenem- and multidrug-resistance in the hospital setting.
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