Abstract
This study was carried out to investigate the epidemiological time-course of New Delhi metallo-beta-lactamase- (NDM-) mediated carbapenem resistance in Enterobacteriaceae in South Korea. A total of 146 non-duplicate NDM-producing Enterobacteriaceae recovered between 2010 and 2015 were voluntarily collected from 33 general hospitals and confirmed by PCR. The species were identified by sequences of the 16S rDNA. Antimicrobial susceptibility was determined either by the disk diffusion method or by broth microdilution, and the carbapenem MICs were determined by agar dilution. Then, multilocus sequence typing and PCR-based replicon typing was carried out. Co-carried genes for drug resistance were identified by PCR and sequencing. The entire genomes of eight random selected NDM producers were sequenced. A total of 69 Klebsiella pneumoniae of 12 sequence types (STs), 34 Escherichia coli of 15 STs, 28 Enterobacter spp. (including one Enterobacter aerogenes), nine Citrobacter freundii, four Raoultella spp., and two Klebsiella oxytoca isolates produced either NDM-1 (n = 126), NDM-5 (n = 18), or NDM-7 (n = 2). The isolates co-produced CTX-M-type ESBL (52.1%), AmpCs (27.4%), additional carbapenemases (7.1%), and/or 16S rRNA methyltransferases (4.8%), resulting in multidrug-resistance (47.9%) or extensively drug-resistance (52.1%). Among plasmids harboring blaNDM, IncX3 was predominant (77.4%), followed by the IncFII type (5.8%). Genome analysis revealed inter-species and inter-strain horizontal gene transfer of the plasmid. Both clonal dissemination and plasmid transfer contributed to the wide dissemination of NDM producers in South Korea.
Highlights
The first New Delhi metallo-beta-lactamase (MBL), New Delhi metallo-beta-lactamase- (NDM-)1, was identified in 2008 in an extensively drug-resistant (XDR) Klebsiella pneumoniae clinical isolate recovered from a urinary specimen of a patient (Yong et al, 2009)
In 2011, five isolates of the same clone were successively identified at the same hospital and one and three NDM-1producing E. coli ST101 isolates were identified at another hospital in Seoul and at a hospital in the southeastern region of the Korean peninsula, respectively
The NDM-1-producing K. pneumoniae ST340 was identified in the central part of the peninsula in 2012 and in 2013, diverse NDM-producing bacterial pathogens such as C. freundii and Enterobacter spp. were identified in a broader region, including the southern peninsula
Summary
The first New Delhi metallo-beta-lactamase (MBL), NDM-1, was identified in 2008 in an extensively drug-resistant (XDR) Klebsiella pneumoniae clinical isolate recovered from a urinary specimen of a patient (Yong et al, 2009). The enzyme had an astonishing range of betalactam substrates, including penicillins, late-generation cephalosporins, and carbapenems with the exception of monobactams (Yong et al, 2009). Further epidemiology revealed that the gene had already spread to various species of bacteria including K. pneumoniae, Escherichia coli, Enterobacter spp., Morganella morganii, and Acinetobacter baumannii throughout the six continents (Johnson and Woodford, 2013), implying that the plasmid encoding NDM has an enormous ability to spread. The NDM subtypes, which differ from the NDM-1 prototype by one to five amino-acid substitutions, exhibit different levels of hydrolyzing activity against carbapenems and other betalactam substrates, depending on the substitutions. Among the first seven subtypes, NDM-7 containing two substitutions of Asp130Asn and Met154Leu has the greatest carbapenemhydrolyzing activity, followed by NDM-5 with Val88Leu and Met154Leu, NDM-6 with Ala233Val, and NDM-1 (Rahman et al, 2014)
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