Molecular features and transmission of NDM-producing Enterobacterales in Israeli Hospitals

NDM-producing Enterobacterales (NDME) account for 34.9% of new carbapenemase-producing Enterobacterales cases in Israeli hospitals. The goals of this study were to characterize the genomic composition of NDME isolates and mobile genetic elements (MGE) and to suggest likely transmission events (TE) of NDME. The study was conducted in three hospital in Israel: the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical centers (TASMC, RMC and SZMC, respectively). All primary isolates of hospitalized patients with NDME-positive Enterobacterales detected between January 2018 and July 2019 were included. Phylogenetic analysis was based on core genome SNP distances excluding recombinations. MGE were classified by comparison of blaNDM gene flanking regions. Post-admission acquisition was defined when NDME was isolated =2 days after admission. Core genome distance of =5 SNPs between isolates from patients with overlapping hospitalization periods was suggestive of potential TE. The study included 212 NDME-positive Enterobacterales isolates from 203 patients, including 104 isolates from TASMC, 30 isolates from RMC and 78 isolates from SZMC. The majority of isolates (n=157, 74%) harbored the blaNDM-1 gene, followed by the blaNDM-5 (n=48) and the blaNDM-15 genes (n=7). The most common NDME species were K. pneumoniae (n=67), E. coli (n=65), E. cloacae complex (n=45) and K. oxytoca (n=14), predominantly revealing a high degree of core genome heterogeneity. The majority of blaNDM-1-harboring isolates (134/157, 85%) were divided into 9 different MGE modules, with varying proportions between species and hospitals. The numbers of post-admission acquisition cases (n=118) that could that be linked to other cases by both molecular and epidemiological criteria were 13/58 (24.2%), 3/48 (6.3%) and 4/12 (33.3%) in TASMC, SZMC and RMC, respectively. The study depicted a complex and highly diverse population structure suggesting that NDME had not spread via clonal expansion but due to the transmission of MGE to already established Enterobacterales clones.