Abstract
Carbapenem-resistant Enterobacterales (CRE) represent a serious threat to public health due to the lack of treatment and high mortality. The rate of antimicrobial resistance of Enterobacterales isolates to major antimicrobials, including carbapenems, is much higher in Vietnam than in Western countries, but the reasons remain unknown due to the lack of genomic epidemiology research. A previous study suggested that carbapenem resistance genes, such as the carbapenemase gene blaNDM, spread via plasmids among Enterobacterales in Vietnam. In this study, we characterized blaNDM-carrying plasmids in Enterobacterales isolated in Vietnam, and identified several possible cases of horizontal transfer of plasmids both within and among species of bacteria. Twenty-five carbapenem-nonsusceptible isolates from a medical institution in Hanoi were sequenced on Illumina short-read sequencers, and 13 blaNDM-positive isolates, including isolates of Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Morganella morganii, and Proteus mirabilis, were further sequenced on an Oxford Nanopore Technologies long-read sequencer to obtain complete plasmid sequences. Almost identical 73 kb IncFII(pSE11)::IncN hybrid plasmids carrying blaNDM-1 were found in a P. mirabilis isolate and an M. morganii isolate. A 112 kb IncFII(pRSB107)::IncN hybrid plasmid carrying blaNDM-1 in an E. coli isolate had partially identical sequences with a 39 kb IncR plasmid carrying blaNDM-1 and an 88 kb IncFII(pHN7A8)::IncN hybrid plasmid in a C. freundii isolate. 148–149 kb IncFIA(Hl1)::IncA/C2 plasmids and 75–76 kb IncFII(Yp) plasmids, both carrying blaNDM-1 were shared among three sequence type 11 (ST11) isolates and three ST395 isolates of K. pneumoniae, respectively. Most of the plasmids co-carried genes conferring resistance to clinically relevant antimicrobials, including third-generation cephalosporins, aminoglycosides, and fluoroquinolones, in addition to blaNDM-1. These results provide insight into the genetic basis of CRE in Vietnam, and could help control nosocomial infections.
Highlights
Carbapenems have a broad spectrum of antimicrobial activity and are reserved for the treatment of infections caused by multidrug-resistant Gram-negative bacteria including Enterobacterales
There was a report that out of 27 carbapenem-resistant Klebsiella pneumoniae isolated from patients in a medical institution in Hanoi, Vietnam from 2014 to 2015, two isolates belonging to sequence type 395 (ST395) harbored blaNDM-1, and five isolates belonging to ST15, ST16, and ST2353 harbored blaNDM-4 [4]
We report the detailed structures of blaNDM-1-carrying plasmids, and co-existing antimicrobial resistance (AMR) genes and mobile gene element (MGE) on the plasmids in Enterobacterales isolated in Vietnam
Summary
Carbapenem-hydrolyzing β-lactamase (carbapenemase) genes, such as blaNDM, blaKPC, and blaOXA-48, that confer resistance to a broad range of β-lactams including third-generation cephalosporins and carbapenems are predominantly encoded on conjugative plasmids and have been transferred among Enterobacterales around the world [3]. There was a report that out of 27 carbapenem-resistant Klebsiella pneumoniae isolated from patients in a medical institution in Hanoi, Vietnam from 2014 to 2015, two isolates belonging to sequence type 395 (ST395) harbored blaNDM-1, and five isolates belonging to ST15, ST16, and ST2353 harbored blaNDM-4 [4]. We previously detected blaNDM in 68.1% (47/69) of CRE isolates from 45 patients in a medical institution in Hanoi, Vietnam from 2010 to 2012, and some of isolates could be shown to transfer blaNDM to Escherichia coli [6], suggesting that blaNDM had spread via plasmids among Enterobacterales in medical institutions and communities in Vietnam
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