Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers

Abstract

In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers (HCCs). Next-generation sequencing was performed on 250 carbapenemase-producing Enterobacteriaceae isolates, including 42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most outbreak isolates were K. pneumoniae (n ϭ 26) and Escherichia coli (n ϭ 11), but 5 isolates comprising three other Enterobacteriaceae species were also cultured. The 26 K. pneumoniae isolates had sequence type 873 (ST873), as did 7 unrelated K. pneumoniae isolates originating from five geographically dispersed HCCs. The 33 ST873 isolates that clustered closely together using whole-genome multilocus sequence typing (wgMLST) carried the same plasmids and had limited differences in the resistome. The 11 E. coli outbreak isolates showed great variety in STs, did not cluster using wgMLST, and showed considerable diversity in resistome and plasmid profiles. The bla NDM-1 gene-carrying plasmid present in the ST873 K. pneumoniae isolates was found in all the other Enterobacteriaceae species cultured at the outbreak location and in a single E. coli isolate from another HCC. We describe a hospital outbreak with an NDM-1-producing K. pneumoniae strain from an unknown source that was also found in patients from five other Dutch HCCs in the same time frame without an epidemiological link. Interspecies transfer of the resistance plasmid was observed in other Enterobacteriaceae species isolated at the outbreak location and in another HCC.

Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

“…The annual number of CPE isolates increased from 49 to 304 (Table 1), meanwhile the number of participating laboratories increased from 40 to 51. During the study period, there were three known outbreaks with CPE: an outbreak in a hospital with 35 bla NDM-1 -positive K. pneumoniae in 2015 [14], an outbreak in a nursing home with eight bla VIM-1positive E. coli in 2017 and one in a hospital with 23 bla NDM-5positive Citrobacter freundii in 2018.…”

“…The predominant STs were ST307 (n ¼ 47), ST873 (n ¼ 37) and ST101 (n ¼ 35) accounting for 31% of all submitted carbapenemase-producing K. pneumoniae isolates. The inclusion of 35 isolates from an outbreak of NDM-1-producing ST873 K. pneumoniae in a Dutch hospital in 2015 caused the abundance of ST873 isolates [14]. ST258, known for its worldwide presence [16], was only found in 11 isolates (3%) in our selection.…”

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

“…Although bla NDM has been found on bacterial chromosomes (82)(83)(84), the vast majority of carriage occurs on plasmids, which play a vital role in dissemination. bla NDM has been reported to be carried on plasmids with a variety of replicon types (33,82,(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104). There are a total of 355 bla NDM -carrying plasmids with complete sequences available in GenBank (accessed on 8 January 2018) (see Data Set S2 in the supplemental material).…”

IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital

“…The reliable reconstruction of transmission chains is therefore essential to the analysis of multispecies outbreaks, although often difficult and laborious (Pirs et al, 2019). Outbreaks of NDM-1-producing Enterobacterales have been reported, as described for the United Kingdom (Fairley et al, 2019), Greece (Politi et al, 2019), Poland (Baraniak et al, 2016), Slovenia (Pirs et al, 2019), Belgium (Heinrichs et al, 2019), Netherlands (Bosch et al, 2017), and most recently Italy (ECDC, 2019). In Europe and more particular in Germany, the prevalence of invasive Enterobacterales with resistance to carbapenems is still low, and NDM-1-producing isolates have only been observed occasionally (Becker et al, 2018b).…”