Abstract
The first hospital outbreak of carbapenemase-producing Enterobacteriaceae in Slovenia occurred in 2014-2016. Whole genome sequencing was used to analyse the population of carbapenem-resistant Klebsiella pneumoniae collected in Slovenia in 2014-2017, including OXA-48 and/or NDM-1 producing strains from the outbreak. A total of 32 K. pneumoniae isolates were analysed using short-read sequencing. Multi-locus sequence typing and core genome multi-locus sequence typing were used to infer genetic relatedness. Antimicrobial resistance markers, virulence factors, plasmid content and wzi types were determined. Long-read sequencing was used for six isolates for detailed analysis of plasmids and their possible transmission. Overall, we detected 10 different sequence types (STs), the most common being ST437 (40.6%). Isolates from the initial outbreak belonged to ST437 (12/16) and ST147 (4/16). A second outbreak of four ST15 isolates was discovered. A new ST (ST3390) and two new wzi types (wzi-556, wzi-559) were identified. blaOXA-48 was found in 17 (53.1%) isolates, blaNDM-1 in five (15.6%), and a combination of blaOXA-48/NDM-1 in seven (21.9%) isolates. Identical plasmids carrying blaOXA-48 were found in outbreak isolates sequenced with long-read sequencing technology. Whole genome sequencing of Slovenian carbapenem-resistant K. pneumoniae isolates revealed multiple clusters of STs, two of which were involved in the first hospital outbreak of carbapenem producing K. pneumoniae in Slovenia. Transmission of the plasmid carrying blaOXA-48 between two STs was likely to have occurred. A previously unidentified second outbreak was also discovered, highlighting the importance of whole genome sequencing in detection and/or characterization of hospital outbreaks and surveillance of drug-resistant bacterial clones.
Highlights
Antimicrobial resistance is a matter of concern worldwide and carbapenemase-producing Enterobacteriaceae (CPE) pose a major threat to human health
Isolates from the initial outbreak belonged to ST437 (12/16) and ST147 (4/16)
Whole genome sequencing of Slovenian carbapenem-resistant K. pneumoniae isolates revealed multiple clusters of STs, two of which were involved in the first hospital outbreak of carbapenem producing K. pneumoniae in Slovenia
Summary
Antimicrobial resistance is a matter of concern worldwide and carbapenemase-producing Enterobacteriaceae (CPE) pose a major threat to human health. In recent years, increased resistance to carbapenems in Klebsiella pneumoniae has been reported in several European countries, with variable distribution of predominant types of carbapenemases [1,3,4]. The most common K. pneumoniae clonal groups (CGs), as defined by multi-locus sequence typing (MLST), which are associated with outbreaks, are CG258 (sequence type (ST) 258 and its derivatives, including ST11, ST340 and ST437), CG14/15, CG17/20, CG43 (including ST101) and ST147 [5]. A recent study shows that the most common clonal lineages in Europe are ST11, ST15, ST101, ST258 and their derivatives [4], and an emerging high-risk clone ST307 [6,7]. High-risk clones ST258, ST14, ST37, ST147 and ST101 are associated with carbapenemase resistance, while ST15 and ST17 usually carry extended spectrum beta-lactamases [8]
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